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Sample records for blind randomised placebo

  1. Cophenylcaine spray vs. placebo in flexible nasendoscopy: a prospective double-blind randomised controlled trial

    NARCIS (Netherlands)

    Georgalas, C.; Sandhu, G.; Frosh, A.; Xenellis, J.

    2005-01-01

    Practices vary across the UK on the use of topical preparation prior to flexible fibreoptic nasendoscopy. In this double-blind study, we randomised 98 patients to receive cophenylcaine or placebo nasal spray before flexible nasendoscopy. A visual analogue scale (1-100) was used to record pain,

  2. Penicillin for acute sore throat : randomised double blind trial of seven days versus three days treatment or placebo in adults

    NARCIS (Netherlands)

    Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA

    2000-01-01

    Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43

  3. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy : a randomised, double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

    Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN

  4. Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

    Directory of Open Access Journals (Sweden)

    E. Tiralongo

    2012-01-01

    Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

  5. Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

    Science.gov (United States)

    Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

    2005-01-01

    Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

  6. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

    Science.gov (United States)

    Stracke, H; Gaus, W; Achenbach, U; Federlin, K; Bretzel, R G

    2008-11-01

    Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

  7. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

    OpenAIRE

    Chetna Deep Lamba; Praveen Oberai; Raj K Manchanda; Padmalaya Rath; P Hima Bindu; Maya Padmanabhan

    2018-01-01

    Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ). Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling t...

  8. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.

    Science.gov (United States)

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-08-01

    To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. RhEPO 40,000 IU fortnightly did not change the course of ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study

    DEFF Research Database (Denmark)

    Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W

    2009-01-01

    BACKGROUND: Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. METHODS: In this randomised, double-blind, placebo-controlled crossover......, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly...... inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. FUNDING: Minster Pharmaceuticals; Lundbeck Foundation....

  10. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Harris, Deborah L; Weston, Philip J; Signal, Matthew; Chase, J Geoffrey; Harding, Jane E

    2013-12-21

    Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35-42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0·57, 95% CI 0·33-0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel

  11. Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Thwaites, Guy E; Scarborough, Matthew; Szubert, Alexander; Nsutebu, Emmanuel; Tilley, Robert; Greig, Julia; Wyllie, Sarah A; Wilson, Peter; Auckland, Cressida; Cairns, Janet; Ward, Denise; Lal, Pankaj; Guleri, Achyut; Jenkins, Neil; Sutton, Julian; Wiselka, Martin; Armando, Gonzalez-Ruiz; Graham, Clive; Chadwick, Paul R; Barlow, Gavin; Gordon, N Claire; Young, Bernadette; Meisner, Sarah; McWhinney, Paul; Price, David A; Harvey, David; Nayar, Deepa; Jeyaratnam, Dakshika; Planche, Tim; Minton, Jane; Hudson, Fleur; Hopkins, Susan; Williams, John; Török, M Estee; Llewelyn, Martin J; Edgeworth, Jonathan D; Walker, A Sarah

    2018-02-17

    Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute

  12. Increasing work-place healthiness with the probiotic Lactobacillus reuteri: A randomised, double-blind placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Stan Vlaicu

    2005-11-01

    Full Text Available Abstract Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730 on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-workers that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo. Results In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p L. reuteri group (p L. reuteri group(p

  13. Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Morice, Alyn H; McGarvey, Lorcan; Pavord, Ian D; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S

    2017-07-01

    To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. ClinicalTrials.gov: NCT01656668.

  14. Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

    Science.gov (United States)

    Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

    2009-01-01

    To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

  15. Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

    Science.gov (United States)

    Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

    2017-11-24

    Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

    Directory of Open Access Journals (Sweden)

    Clive Ballard

    2008-04-01

    Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

  17. Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial

    NARCIS (Netherlands)

    Martinez de Tejada, B.; Karolinski, A.; Ocampo, M. C.; Laterra, C.; Hösli, I.; Fernández, D.; Surbek, D.; Huespe, M.; Drack, G.; Bunader, A.; Rouillier, S.; López de Degani, G.; Seidenstein, E.; Prentl, E.; Antón, J.; Krähenmann, F.; Nowacki, D.; Poncelas, M.; Nassif, J. C.; Papera, R.; Tuma, C.; Espoile, R.; Tiberio, O.; Breccia, G.; Messina, A.; Peker, B.; Schinner, E.; Mol, B. W.; Kanterewicz, L.; Wainer, V.; Boulvain, M.; Othenin-Girard, V.; Bertolino, M. V.; Irion, O.; Tellenbach, M.; Vögele, E.; Azbar, R.; Raggi, A.; Birkenmaier, A.; Kann, S.; Scheibner, K.; Huguelet, M.; Amann, E.; Baumann, M.; Jakob, E.; Biedermann, K.; Hodel, M.; Fischer, T.; Pfau, K.; Estermann, K.

    2015-01-01

    To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to

  18. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

    DEFF Research Database (Denmark)

    Juul, Anne Benedicte; Wetterslev, Jørn; Gluud, Christian

    2006-01-01

    Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University...

  19. Heart rate acceleration with GLP-1 receptor agonists in type 2 diabetes patients : an acute and 12-week randomised, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, T.; Kramer, Mark H H; Diamant, Michaela; van Raalte, Daniël H

    OBJECTIVE: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. DESIGN: Acute and 12-week randomised, placebo-controlled, double-blind, single-centre, parallel-group trial. METHODS: In total, 57 type 2 diabetes patients

  20. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

    OpenAIRE

    Villar-Garc?a, Judit; G?erri-Fern?ndez, Robert; Moya, Andr?s; Gonz?lez, Alicia; Hern?ndez, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D?Auria, Giuseppe; Knobel, Hernando

    2017-01-01

    Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly ...

  1. Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

    Science.gov (United States)

    Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

    2013-01-01

    Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

  2. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

    Directory of Open Access Journals (Sweden)

    Chetna Deep Lamba

    2018-01-01

    Full Text Available Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ. Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling the eligibility criteria were enrolled (n = 60 and randomised to either the homoeopathic intervention (HI (n = 30 or identical placebo (P (n = 30 with uniform lifestyle modification (LSM for 6 months. Results: The menstrual regularity with improvement in other signs/symptoms was observed in 60% of the cases (n = 18 in HI + LSM group and none (n = 0 in control group (P = 0.001. Statistically significant difference (P = 0.016 was observed in reduction of intermenstrual duration (from 76.1 ± 37.7 to 46.6 ± 38.7 days in HI + LSM in comparison to placebo + LSM group (from 93.0 ± 65.2 to 93.9 ± 96.2 days. In PCOSQ, also, significant improvement was observed in HI group in domains of weight, fertility, emotions and menstrual problems (P < 0.05 with no difference in body hair (P = 0.708. No change was observed in respect of improvement in the ultrasound findings. Pulsatilla was the most frequently indicated medicine (n = 12, 40%. Conclusion: HI along with LSM has shown promising outcome; further comparative study with standard conventional treatment on adequate sample size is desirable.

  3. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

    2015-02-01

    Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

  4. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial

    NARCIS (Netherlands)

    S. Koning (Sander); L.W.A. van Suijlekom-Smit (Lisette); J.L. Nouwen (Jan); C.M. Verduin (Cees); R.M.D. Bernsen (Roos); A.P. Oranje (Arnold); S. Thomas (Siep); J.C. van der Wouden (Hans)

    2002-01-01

    textabstractOBJECTIVE: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. DESIGN: Randomised placebo controlled trial. SETTING: General practices in Greater Rotterdam.

  5. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

    Science.gov (United States)

    Barnes, Thomas R E; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom K J; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

    2016-04-01

    Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. Adult psychiatric services, treating people with schizophrenia. Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week

  6. Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Esmael Habtamu, PhD

    2018-05-01

    Full Text Available Summary: Background: Trachomatous trichiasis is treated surgically to prevent sight loss. Unfavourable surgical outcomes remain a major challenge. We investigated the hypothesis that doxycycline might reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis through anti-matrix metalloproteinase and anti-inflammatory activity. Methods: In this randomised, double-blind, placebo-controlled trial, adults (aged >18 years with upper lid trachomatous trichiasis in association with tarsal conjunctive scarring were recruited through community-based screening and surgical outreach campaigns in Ethiopia. Individuals who had previously had eyelid surgery were excluded. Participants were randomly assigned (1:1, with random block sizes of four or six, to receive oral doxycycline (100 mg once a day or placebo for 28 days immediately after trichiasis surgery. Randomisation was stratified by surgeon. Patients, investigators, surgeons, and all other study team members were masked to study group allocation and treatment. Participants were examined at 10 days, and 1, 6, and 12 months after surgery. The primary outcome was the cumulative proportion of individuals who developed postoperative trichiasis by 12 months. Primary analyses were done in all participants who attended at least one of the four follow-up assessments. Safety analyses were done in all participants who attended either the 10 day or 1 month follow-up assessments. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201512001370307. Findings: Between Dec 21, 2015, and April 6, 2016, 1000 patients with trichiasis were enrolled and randomly assigned to treatment (499 patients to doxycycline, 501 patients to placebo. All but one participant attended at least one follow-up assessment. Thus, 999 participants were assessed for the primary outcome: 498 in the doxycycline group and 501 in the placebo group. By month 12, 58 (12% of

  7. The efficacy of Femal in women with premenstrual syndrome: a randomised, double-blind, parallel-group, placebo-controlled, multicentre study

    DEFF Research Database (Denmark)

    Gerhardsen, G.; Hansen, A.V.; Killi, M.

    2008-01-01

    Introduction: A double-blind, placebo-controlled, randomised, parallel-group, multicentre study was conducted to evaluate the effect of a pollen-based herbal medicinal product, Femal (R) (Sea-Band Ltd, Leicestershire, UK), on premenstrual sleep disturbances (PSD) in women with premenstrual syndrome...... as the main symptom cluster makes this herbal medicinal product a promising addition to the therapeutic arsenal for women with PMS Udgivelsesdato: 2008/6...

  8. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

    Science.gov (United States)

    Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

    2016-11-15

    Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

  9. Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea.

    Science.gov (United States)

    Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

    2011-01-01

    OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation.

  10. Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Evans, Malkanthi; Salewski, Ryan P; Christman, Mary C; Girard, Stephanie-Anne; Tompkins, Thomas A

    2016-07-01

    Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

  11. Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.

    Science.gov (United States)

    Impey, Lawrence; Pandit, Meghana

    2005-05-01

    External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. Randomised, double-blinded, placebo-controlled trial. UK teaching hospital. One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV. Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat. Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity. The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged. The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.

  12. Randomised double blind placebo controlled trial on Lactobacillus reuteri DSM 17938: improvement in symptoms and bowel habit in functional constipation.

    Science.gov (United States)

    Riezzo, G; Orlando, A; D'Attoma, B; Linsalata, M; Martulli, M; Russo, F

    2018-01-29

    Dysbiosis may contribute to constipation and its symptoms, therefore probiotic administration could improve significantly gut health and functions. The aim of the study was to investigate the effects of a long-lasting administration of Lactobacillus reuteri DSM 17938 (LR DSM 17938) on symptoms and quality of life (QoL) score in patients with functional constipation (FC). 56 FC patients with normal colonic transit time and without anorectal disorders and pelvic floor dysfunctions completed the study. LR DSM 17938 was administered for 105 days in a randomised double-blind clinical trial (28 patients per arm). Individual and cumulative scores including the Constipaq, a modified Constipation Scoring System (CSS) that considers the patient assessment of constipation-QoL (PAC-QoL), were calculated during the preliminary visit (V0), at day 15 (end of the induction period with a LR DSM 17938 double dosage, 4×10 8 cfu), day 60 (intermediate evaluation) and day 105 (V4) after a standard dosage (2×10 8 cfu). At the end of treatment, the beneficial effect of LR DSM 17938 compared to placebo was significantly evident for symptoms related to gas content and dysbiosis (abdominal discomfort, pain and bloating), incomplete defecation and helps for defecation (PDSM 17938 treatment, a marked and positive effect on both the CSS single and the cumulative items was evident with the exception of unfruitful attempt and Bristol score. Present findings indicate that LR DSM 17938 has an effect on symptoms different from stool consistency, and they suggest that this probiotic can effectively be used in association therapy rather than as single-drug therapy in the management of FC.

  13. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration

    International Nuclear Information System (INIS)

    Brooker, Sonja; Martin, Susan; Pearson, Ann; Bagchi, Debasis; Earl, Judith; Gothard, Lone; Hall, Emma; Porter, Lucy; Yarnold, John

    2006-01-01

    Background and purpose: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. Patients and methods: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n=44) or placebo (n=22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm 2 ) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. Results: At 12 months post-randomisation, ≥50% reduction in surface area (cm 2 ) of breast induration was recorded in13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. Conclusions: The study failed to show efficacy of orally-adminstered GSPE in patients with breast induration following radiotherapy for breast cancer

  14. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

    2016-11-01

    Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

  15. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Vollert, Jan

    2014-01-01

    In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

  16. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W

    2016-01-01

    OBJECTIVE: To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial...... design conducted at eight hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1...... weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943; Results....

  17. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bussel, James B; Provan, Drew; Shamsi, Tahir; Cheng, Gregory; Psaila, Bethan; Kovaleva, Lidia; Salama, Abdulgabar; Jenkins, Julian M; Roychowdhury, Debasish; Mayer, Bhabita; Stone, Nicole; Arning, Michael

    2009-02-21

    Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; ptime during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

  18. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

    2013-09-01

    Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0

  19. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

    2008-11-01

    Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

  20. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

    Science.gov (United States)

    le Roux, Carel W; Astrup, Arne; Fujioka, Ken; Greenway, Frank; Lau, David C W; Van Gaal, Luc; Ortiz, Rafael Violante; Wilding, John P H; Skjøth, Trine V; Manning, Linda Shapiro; Pi-Sunyer, Xavier

    2017-04-08

    Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m 2 , or at least 27 kg/m 2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, pprediabetes. Novo Nordisk, Denmark. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Motokazu Kato

    Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

  2. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

    2008-06-01

    Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

  3. Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)

    DEFF Research Database (Denmark)

    Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup

    2015-01-01

    are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points......INTRODUCTION: Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often...... have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process...

  4. Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Sarris Jerome

    2012-12-01

    Full Text Available Abstract Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16, three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender. Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022 and enhanced mood (p=.027. The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin

  5. Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bines, Julie E; Danchin, Margaret; Jackson, Pamela; Handley, Amanda; Watts, Emma; Lee, Katherine J; West, Amanda; Cowley, Daniel; Chen, Mee-Yew; Barnes, Graeme L; Justice, Frances; Buttery, Jim P; Carlin, John B; Bishop, Ruth F; Taylor, Barry; Kirkwood, Carl D

    2015-12-01

    Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; pvaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; pvaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. RV3-BB vaccine was

  6. A Double-Blind, Randomised, Placebo-Controlled Trial of EMLA® Cream (Eutectic Lidocaine/Prilocaine Cream) for Analgesia Prior to Cryotherapy of Plantar Warts in Adults.

    Science.gov (United States)

    Lee, Siew Hui; Pakdeethai, Janthorn; Toh, Matthias P H S; Aw, Derrick C W

    2014-10-01

    Cryotherapy with liquid nitrogen is an effective, safe and convenient form of treatment for plantar warts. EMLA® cream (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is a topical local anaesthetic agent that has proven to be effective and well tolerated in the relief of pain associated with various minor interventions in numerous clinical settings. In a single-centre, double-blind, randomised placebo-controlled study, 64 subjects were randomised into 2 groups. The subjects had a thick layer of EMLA® cream or placebo cream applied to pared plantar wart(s) and onto the surrounding margin of 1 mm to 2 mm under occlusion for 60 minutes prior to receiving cryotherapy. The pain of cryotherapy was evaluated by the subjects using a self-administered Visual Analogue Scale (VAS) immediately after the cryotherapy. There was no statistical difference between the mean VAS score for EMLA® cream (47.0 ± 21.4 mm) and placebo (48.9 ± 22.0 mm). Those with more than 1 wart had a significantly higher VAS score than those with only 1 wart (59.1 ± 21.8 vs. 44.3 ± 20.4, P cryotherapy. We conclude that the application of EMLA® cream prior to cryotherapy does not reduce the pain associated with cryotherapy.

  7. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

    2011-09-01

    There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

    Science.gov (United States)

    Kim, Jong S; Lee, Eun-Jae; Chang, Dae-Il; Park, Jong-Ho; Ahn, Seong Hwan; Cha, Jae-Kwan; Heo, Ji Hoe; Sohn, Sung-Il; Lee, Byung-Chul; Kim, Dong-Eog; Kim, Hahn Young; Kim, Seongheon; Kwon, Do-Young; Kim, Jei; Seo, Woo-Keun; Lee, Jun; Park, Sang-Won; Koh, Seong-Ho; Kim, Jin Young; Choi-Kwon, Smi

    2017-01-01

    Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the

  9. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

    2015-12-03

    This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in

  10. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

    Science.gov (United States)

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-09-01

    Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

  11. A randomised, double blind, placebo-controlled, multi-centric parallel arm trial to assess the effects of homoeopathic medicines on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Raj K Manchanda

    2014-01-01

    Full Text Available Background: Chronic rhinosinusitis (CRS is one of the most common illnesses interfering with patient′s quality of life and work. Observational studies conducted by the Council indicate positive outcome. This protocol has been developed to ascertain the usefulness of homoeopathic intervention in comparison with control group in a randomised control setting. Objectives: Primary objective is to evaluate the changes in TSS (Total Symptoms Score and SNOT-22 (Sino-nasal Outcome Test-22 within the two groups of the study (Homoeopathy + Placebo. Secondary objective is to evaluate changes in SNOT-22 at end of the trial, changes in Lund and Mackay staging of CT scan, rhinoscopy grading, absolute eosinophil count, global assessment by investigator and patient, and number of acute exacerbations of CRS (for frequency, duration and intensity as per TSS scale compared to placebo. Methods/Design: This is a randomised double blind, placebo-controlled, multi-centric parallel arm trial of 6 months (three months treatment and three months observation period with 14 days run-in period. The primary outcome is a composite of the changes in the TSS and SNOT-22 over 3 months from baseline with area under the curve and changes over 3 months in the Sinus Nasal Outcome Test 22 (SNOT-22 from baseline. Prescription shall be made as per the homoeopathic principles. Efficacy data will be analysed in the intention-to-treat population. Discussion: This trial will help to evaluate the efficacy of homoeopathic individualised treatment using LM-potencies versus placebo in patients suffering from CRS as per the homoeopathic dictum.

  12. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

    2013-12-01

    Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; pcholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

    Science.gov (United States)

    Garly, May-Lill; Balé, Carlitos; Martins, Cesário Lourenco; Whittle, Hilton C; Nielsen, Jens; Lisse, Ida M; Aaby, Peter

    2006-12-16

    To investigate whether prophylactic antibiotics can prevent complications of measles. Community based, randomised, double blind, placebo controlled trial. Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. Clinical trials NCT00168532.

  14. Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

    Science.gov (United States)

    Blanco-Rojo, Ruth; Pérez-Granados, Ana M; Toxqui, Laura; González-Vizcayno, Carmen; Delgado, Marco A; Vaquero, M Pilar

    2011-06-01

    Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

  15. Role of oral tramadol 50 mg in reducing pain associated with outpatient hysteroscopy: A randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Hassan, AbdelGany; Haggag, Hisham

    2016-02-01

    Several drugs have been used to reduce hysteroscopy-associated pain. Although the Royal College of Obstetricians and Gynaecologists has recommended against the use of opiates in outpatient hysteroscopy, we wished to investigate if opioids can be used if the appropriate opioid was given in the appropriate dose. To study the effectiveness of tramadol 50 mg in reducing pain associated with outpatient hysteroscopy. A prospective randomised double-blind placebo-controlled trial conducted in the outpatient hysteroscopy clinic at Cairo University Hospital. Main outcome measures were the severity of pain during the procedure, immediately after the procedure and 30 minutes later assessed by a visual analogue scale (VAS). VAS of 0 indicates no pain and VAS of 10 indicates the worst possible pain. A total of 140 women who had diagnostic outpatient hysteroscopy were randomised to receive oral tramadol 50 mg or placebo one h before performing outpatient hysteroscopy. There was no difference between the groups in the age, parity, duration of the procedures or indications of hysteroscopy. The median pain score was significantly lower in the tramadol group during the procedure (5 vs 6; P = 0.013), immediately after the procedure (3 vs 4; P pain evoked by the procedure and the drug was well tolerated by women. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  16. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

    2016-05-01

    Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; pbotulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a

  17. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Bruix, Jordi; Qin, Shukui; Merle, Philippe; Granito, Alessandro; Huang, Yi-Hsiang; Bodoky, György; Pracht, Marc; Yokosuka, Osamu; Rosmorduc, Olivier; Breder, Valeriy; Gerolami, René; Masi, Gianluca; Ross, Paul J; Song, Tianqiang; Bronowicki, Jean-Pierre; Ollivier-Hourmand, Isabelle; Kudo, Masatoshi; Cheng, Ann-Lii; Llovet, Josep M; Finn, Richard S; LeBerre, Marie-Aude; Baumhauer, Annette; Meinhardt, Gerold; Han, Guohong

    2017-01-07

    There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1-12·1) for regorafenib versus 7·8 months (6·3-8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group

  18. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    H Asita de Silva

    2011-05-01

    Full Text Available Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial.In total, 1,007 patients were randomized, using a 2 × 2 × 2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously, promethazine (25 mg intravenously, and hydrocortisone (200 mg intravenously, each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75% patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25-67 at 1 h and by 38% (95% CI 26-49 up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.

  19. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Landewé, Robert B. M.; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T.; Zhou, Yiying; Hsia, Elizabeth C.; Doyle, Mittie K.

    2012-01-01

    The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of

  20. A randomised, double-blind, placebo-controlled, multicentre study of the safety and efficacy of BIOBYPASS (AdGVVEGF121.10NH) gene therapy in patients with refractory advanced coronary artery disease: the NOVA trial

    DEFF Research Database (Denmark)

    Kastrup, Jens; Jørgensen, Erik; Fuchs, Shmuel

    2011-01-01

    Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH])....

  1. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

    2014-10-04

    Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

  2. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

    Science.gov (United States)

    Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan

    2015-01-01

    Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; Protavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients

  3. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Ole

    2010-01-01

    OBJECTIVE: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. METHODS: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment....

  4. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Lars Ole

    2010-01-01

    Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. Methods A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n= 167) or saline (n= 170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention...

  5. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Faghihzadeh, Forouzan; Adibi, Payman; Hekmatdoost, Azita

    2015-09-14

    Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

  6. Radial extracorporeal shock-wave therapy in patients with chronic rotator cuff tendinitis: a prospective randomised double-blind placebo-controlled multicentre trial.

    Science.gov (United States)

    Kolk, A; Yang, K G Auw; Tamminga, R; van der Hoeven, H

    2013-11-01

    The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were randomly allocated to a treatment group who received low-dose rESWT (three sessions at an interval 10 to 14 days, 2000 pulses, 0.11 mJ/mm(2), 8 Hz) or to a placebo group, with a follow-up of six months. The patients and the treating orthopaedic surgeon, who were both blinded to the treatment, evaluated the results. A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group. A visual analogue scale (VAS) score for pain, a Constant-Murley (CMS) score and a simple shoulder test (SST) score significantly improved in both groups at three and six months compared with baseline (all p ≤ 0.012). The mean VAS was similar in both groups at three (p = 0.43) and six months (p = 0.262). Also, the mean CMS and SST scores were similar in both groups at six months (p = 0.815 and p = 0.834, respectively). It would thus seem that low-dose rESWT does not reduce pain or improve function in patients chronic rotator cuff tendinitis compared with placebo treatment.

  7. Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study.

    Science.gov (United States)

    Bouroubi, Athmane; Donazzolo, Yves; Donath, Franck; Eccles, Ron; Russo, Marc; Harambillet, Nadine; Gautier, Stéphanie; Montagne, Agnès

    2017-09-01

    The aim of this study was to compare the efficacy and safety of a new oromucosal ibuprofen form, ibuprofen 25 mg lozenge, in single and repeat dosing for up to 4 days, to the matched placebo, in the treatment of acute sore throat pain in adults. In this randomised, double-blind, placebo-controlled trial, adult patients with non-streptococcal sore throat and signs of moderate-to-severe associated pain (≥5 on the objective Tonsillo-Pharyngitis Assessment 21-point scale and ≥60 mm on the subjective 0-100 mm visual analogue Sore Throat Pain Intensity Scale [STPIS]) were assigned ibuprofen 25 mg (n=194) or matching placebo (n=191) lozenge treatment. Efficacy was assessed (at the investigating centre up to 2 hours after first dosing, then on an ambulatory basis) by parameters derived from patient's scores on scales of pain relief, pain intensity, and global efficacy assessment. The primary efficacy end-point was the time-weighted TOTal PAin Relief (TOTPAR) over 2 hours after first dosing using the Sore Throat Relief Scale (STRS). Safety and local tolerability were assessed. Ibuprofen 25 mg was superior to placebo on numerous pain relief parameters; TOTPAR was significantly higher with ibuprofen 25 mg over 2 hours after first dosing (Ppain (n=128), after an average 4 days (Prelief of sore throat pain and is as well tolerated as placebo. ClinicalTrials.gov, NCT01785862. © 2017 John Wiley & Sons Ltd.

  8. A poly-herbal blend (Herbagut®) on adults presenting with gastrointestinal complaints: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Lopresti, Adrian L; Gupta, Hemant; Smith, Stephen J

    2018-03-20

    To evaluate the efficacy and tolerability of a poly-herbal formulation, Herbagut, for the treatment of gastrointestinal symptoms and its effect on quality of life parameters in patients presenting with self-reported, unsatisfactory bowel habits. This was a randomised, double-blind, placebo-controlled trial. Fifty adults with self-reported unsatisfactory bowel habits, primarily characterised by chronic constipation were randomly allocated to take Herbagut or a matching placebo for 28 days. Efficacy of gastrointestinal changes was measured by the completion of a patient daily diary evaluating changes in stool type (Bristol Stool Form Scale), ease of bowel movements, and feeling of complete evacuation; and the Gastrointestinal Symptom Rating Scale (GSRS). Changes in quality of life were also examined using the World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF), and the Patient Assessment of Constipation-Quality of Life (PAC-QOL). All participants completed the 28-day trial with no adverse events reported. Compared to the placebo, weekly bowel movements increased over time (p pain, constipation, diarrhoea, indigestion, and reflux also decreased significantly in people taking Herbagut compared to placebo (p < .001, for all domains). Moreover, quality of life significantly improved in the Herbagut group compared to placebo as indicated by significantly greater improvement in WHOQOL-BREF domain ratings for overall quality of life, social relations, environmental health, psychological health, and physical health (p < .001, for all domains); and PAC-QOL domain ratings for physical discomfort, psychosocial discomfort, worries and concerns, and life satisfaction (p < .001, for all domains). The changes were considered clinically meaningful as evidenced by their large effect sizes. Herbagut ingestion over a 28-day period resulted in improvements in several gastrointestinal symptoms and overall quality of life. Further investigation

  9. Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

    Science.gov (United States)

    Lockley, Steven W; Dressman, Marlene A; Licamele, Louis; Xiao, Changfu; Fisher, Dennis M; Flynn-Evans, Erin E; Hull, Joseph T; Torres, Rosarelis; Lavedan, Christian; Polymeropoulos, Mihael H

    2015-10-31

    Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist. We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres. We screened totally blind adults (18-75 years of age), who were eligible for the randomisation phase of SET if they had a non-24-hour circadian period (τ) of 24·25 h or longer (95% CI greater than 24·0 and up to 24·9 h), as calculated from measurements of urinary 6-sulphatoxymelatonin rhythms. For SET, we used block randomisation to assign patients (1:1) to receive tasimelteon (20 mg) or placebo every 24 h at a fixed clock time 1 h before target bedtime for 26 weeks. Patients who entered the open-label group receiving tasimelteon in SET or who did not meet the SET inclusion criteria but did meet the RESET inclusion criteria were screened for RESET. A subset of the patients who entered the open-label group before the RESET study and who had eligible τ values were screened for RESET after completing the open-label treatment. In RESET, we withdrew tasimelteon in a randomised manner (1:1) in patients who responded (ie, entrained) after a tasimelteon run-in period. Entrainment was defined as having τ of 24·1 h or less and a 95% CI that included 24·0 h. In SET, the primary endpoint was the proportion of entrained patients, assessed in the intention-to-treat population. The planned step-down primary endpoint assessed the proportion of patients who had a clinical response (entrainment at month 1 or month 7 plus clinical improvement, measured by the Non-24 Clinical Response Scale). In RESET, the primary endpoint was the proportion of non

  10. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome

    Science.gov (United States)

    Klupp, Nerida L.; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z.; Chang, Dennis H.

    2016-01-01

    This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [−0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [−0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742

  11. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

    Science.gov (United States)

    Cuzick, Jack; Sestak, Ivana; Forbes, John F; Dowsett, Mitch; Knox, Jill; Cawthorn, Simon; Saunders, Christobel; Roche, Nicola; Mansel, Robert E; von Minckwitz, Gunter; Bonanni, Bernardo; Palva, Tiina; Howell, Anthony

    2014-03-22

    Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, pbreast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in

  12. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Krug, Lee M; Kindler, Hedy L; Calvert, Hilary; Manegold, Christian; Tsao, Anne S; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E E; Fukuoka, Kazuya; Gaafar, Rabab M; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A; Lubiniecki, Gregory M; Sun, Xing; Smith, Margaret; Baas, Paul

    2015-04-01

    Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). In this randomised trial, vorinostat given as a second-line or third

  13. Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

    Science.gov (United States)

    Bennell, Kim; Coburn, Sally; Wee, Elin; Green, Sally; Harris, Anthony; Forbes, Andrew; Buchbinder, Rachelle

    2007-01-01

    Background Chronic rotator cuff pathology (CRCP) is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI), average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36), Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log

  14. Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Harris Anthony

    2007-08-01

    Full Text Available Abstract Background Chronic rotator cuff pathology (CRCP is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI, average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36, Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health

  15. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

    NARCIS (Netherlands)

    Moll, Etelka; Bossuyt, Patrick M. M.; Korevaar, Johanna C.; Lambalk, Cornelis B.; van der Veen, Fulco

    2006-01-01

    OBJECTIVE: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. DESIGN: Randomised clinical trial. SETTING: Multicentre trial in 20 Dutch hospitals. PARTICIPANTS: 228 women with polycystic ovary

  16. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Armah, George E; Sow, Samba O; Breiman, Robert F; Dallas, Michael J; Tapia, Milagritos D; Feikin, Daniel R; Binka, Fred N; Steele, A Duncan; Laserson, Kayla F; Ansah, Nana A; Levine, Myron M; Lewis, Kristen; Coia, Michele L; Attah-Poku, Margaret; Ojwando, Joel; Rivers, Stephen B; Victor, John C; Nyambane, Geoffrey; Hodgson, Abraham; Schödel, Florian; Ciarlet, Max; Neuzil, Kathleen M

    2010-08-21

    Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting

  17. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial.

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    A James Daveson

    Full Text Available BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. TRIAL REGISTRATION: ClinicalTrials.gov NCT00671138.

  18. Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Martinez de Tejada, B; Karolinski, A; Ocampo, M C; Laterra, C; Hösli, I; Fernández, D; Surbek, D; Huespe, M; Drack, G; Bunader, A; Rouillier, S; López de Degani, G; Seidenstein, E; Prentl, E; Antón, J; Krähenmann, F; Nowacki, D; Poncelas, M; Nassif, J C; Papera, R; Tuma, C; Espoile, R; Tiberio, O; Breccia, G; Messina, A; Peker, B; Schinner, E; Mol, B W; Kanterewicz, L; Wainer, V; Boulvain, M; Othenin-Girard, V; Bertolino, M V; Irion, O

    2015-01-01

    To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour. © 2014 Royal College of Obstetricians and Gynaecologists.

  19. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Villar-García, Judit; Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P; Artacho, Alejandro; D Auria, Giuseppe; Knobel, Hernando

    2017-01-01

    Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome

  20. The effects of topical heat therapy on chest pain in patients with acute coronary syndrome: a randomised double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Mohammadpour, Ali; Mohammadian, Batol; Basiri Moghadam, Mehdi; Nematollahi, Mahmoud Reza

    2014-12-01

    To investigate the effects of local heat therapy on chest pain in patients with acute coronary syndrome. Chest pain is a very common complaint in patients with acute coronary syndrome. It is managed both pharmacologically and nonpharmacologically. Pharmacological pain management is associated with different side effects. This was a randomised double-blind placebo-controlled clinical trial conducted in 2013. A convenience sample of 66 patients with acute coronary syndrome was selected from a coronary care unit of a local teaching hospital affiliated to Gonabad University of Medical Sciences, Gonabad, Iran. Patients were randomly assigned to either the experimental or the placebo group. Patients in the experimental and the placebo groups received local heat therapy using a hot pack warmed to 50 and 37 °C, respectively. We assessed chest pain intensity, duration and frequency as well as the need for opioid analgesic therapy both before and after the study. The study instrument consisted of a demographic questionnaire, the McGill Pain Questionnaire, and a data sheet for documenting pain frequency and duration as well as the need for analgesic therapy. The placebo heat therapy did not significantly decrease the intensity, the duration and the frequency of pain episodes. However, pain intensity, duration and frequency in the experimental group decreased significantly after the study. Moreover, the groups differed significantly in terms of the need for opioid analgesic therapy neither before nor after the intervention. Local heat therapy is an effective intervention for preventing and relieving chest pain in patients with acute coronary syndrome. Effective pain management using local heat therapy could help nurses play an important role in providing effective care to patients with acute coronary syndrome and in minimising adverse effects associated with pain medications. © 2014 John Wiley & Sons Ltd.

  1. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study.

    Science.gov (United States)

    Dimopoulos, Meletios; Siegel, David S; Lonial, Sagar; Qi, Junyuan; Hajek, Roman; Facon, Thierry; Rosinol, Laura; Williams, Catherine; Blacklock, Hilary; Goldschmidt, Hartmut; Hungria, Vania; Spencer, Andrew; Palumbo, Antonio; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Sun, Linda; Vuocolo, Scott; Anderson, Kenneth C

    2013-10-01

    We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most

  2. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Kil, Jonathan; Lobarinas, Edward; Spankovich, Christopher; Griffiths, Scott K; Antonelli, Patrick J; Lynch, Eric D; Le Prell, Colleen G

    2017-09-02

    Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these

  3. Efficacy of Bacillus coagulans Unique IS2 in treatment of irritable bowel syndrome in children: a double blind, randomised placebo controlled study.

    Science.gov (United States)

    Sudha, M Ratna; Jayanthi, N; Aasin, M; Dhanashri, R D; Anirudh, T

    2018-04-26

    The efficacy of the probiotic strain, Bacillus coagulans Unique IS2 in the treatment of Irritable Bowel Syndrome (IBS) was evaluated in children. A total of 141 children of either sex in the age group 4-12 years, diagnosed with IBS according to the Rome III criteria, participated in the double-blind randomised controlled trial. Children received either B. coagulans Unique IS2 chewable tablets or placebo once daily for eight weeks followed by a two week follow-up period. Reduction in pain intensity as well as other symptoms associated with Irritable Bowel Syndrome like abdominal discomfort, bloating, distension, sense of incomplete evacuation, straining at stool, urgency of bowel movement, passage of gas and mucus, and bowel habit satisfaction were assessed. B. coagulans Unique IS2 treated group showed a greater reduction in pain scores as evaluated by a weekly pain intensity scale. There was a significant reduction (Pcoagulans Unique IS2 treated group as compared to the placebo group. This study demonstrates the efficacy of B. coagulans Unique IS2 in reducing the symptoms of Irritable Bowel Syndrome in children in the age group of 4-12 years.

  4. Chronic Effects of a Wild Green Oat Extract Supplementation on Cognitive Performance in Older Adults: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    Directory of Open Access Journals (Sweden)

    Narelle M. Berry

    2012-05-01

    Full Text Available Background and aim: Preliminary evaluation of a wild green oat extract (WGOE (Neuravena® ELFA®955, Frutarom, Switzerland revealed an acute cognitive benefit of supplementation. This study investigated whether regular daily WGOE supplementation would result in sustained cognitive improvements. Method: A 12-week randomised, double-blind, placebo-controlled cross-over trial of WGOE supplementation (1500 mg/day versus placebo was undertaken in 37 healthy adults aged 67 ± 0.8 years (mean ± SEM. Cognitive assessments included the Stroop colour-word test, letter cancellation, the rule-shift task, a computerised multi-tasking test battery and the trail-making task. All assessments were conducted in Week 12 and repeated in Week 24 whilst subjects were fasted and at least 18 h after taking the last dose of supplement. Result: Chronic WGOE supplementation did not affect any measures of cognition. Conclusion: It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment.

  5. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Li, Jin; Qin, Shukui; Xu, Ruihua; Yau, Thomas C C; Ma, Brigette; Pan, Hongming; Xu, Jianming; Bai, Yuxian; Chi, Yihebali; Wang, Liwei; Yeh, Kun-Huei; Bi, Feng; Cheng, Ying; Le, Anh Tuan; Lin, Jen-Kou; Liu, Tianshu; Ma, Dong; Kappeler, Christian; Kalmus, Joachim; Kim, Tae Won

    2015-06-01

    In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib

  6. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Jean-Yves Reginster

    2013-01-01

    Full Text Available Objective. Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis.Methods. Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW 2.5-5 mm were randomly allocated to strontium ranelate 1 g/day (n=558, 2 g/day (n=566 or placebo (n=559. The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC score, and knee pain. The trial is registered (ISRCTN41323372.Results. The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56 mm; 2 g/day: -0.27 (SD 0.63 mm; placebo:-0.37 (SD 0.59 mm; treatment-placebo differences were 0.14 (SE 0.04, 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04, 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed withstrontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day. There were greater reductions in total WOMAC score (p=0.045, pain subscore (p=0.028, physical function subscore (p=0.099 and knee pain (p=0.065 with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions. Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.Additional supplementary data are published online only. To view these files please visit the journal online (http://dx.doi. org/10.1136/annrheumdis-2012-202231

  7. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Sun, Hong; Dodick, David W; Silberstein, Stephen; Goadsby, Peter J; Reuter, Uwe; Ashina, Messoud; Saper, Joel; Cady, Roger; Chon, Yun; Dietrich, Julie; Lenz, Robert

    2016-04-01

    The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3·4 (SE 0·4) days with AMG 334 70 mg versus -2·3 (0·3) days with placebo (difference -1·1 days [95% CI -2·1 to -0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (-2·2 [SE 0·4]) and the 21 mg (-2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54

  8. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

    Science.gov (United States)

    Norman, Jane E; Mackenzie, Fiona; Owen, Philip; Mactier, Helen; Hanretty, Kevin; Cooper, Sarah; Calder, Andrew; Mires, Gary; Danielian, Peter; Sturgiss, Stephen; MacLennan, Graeme; Tydeman, Graham; Thornton, Steven; Martin, Bill; Thornton, James G; Neilson, James P; Norrie, John

    2009-06-13

    Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

  9. Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Mark Lown

    Full Text Available High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME, may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut.A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract.Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC (glucose (mmol / L x h for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316, -14.0% (-26.0%, -2.0%; p = 0.022 and -22.0% (-33.9%, -10.0%; p<0.001 respectively. The difference in the pIAUC (insulin (mIU / L x h for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234, -23.8% (-39.9%, -7.8%; p = 0.004 and -24.7% (-40.8%, -8.6%; p = 0.003 respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence.Mulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a classical dose response curve with

  10. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial.

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    Chiswick, Carolyn; Reynolds, Rebecca M; Denison, Fiona; Drake, Amanda J; Forbes, Shareen; Newby, David E; Walker, Brian R; Quenby, Siobhan; Wray, Susan; Weeks, Andrew; Lashen, Hany; Rodriguez, Aryelly; Murray, Gordon; Whyte, Sonia; Norman, Jane E

    2015-10-01

    Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs ≥40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0·029, 95% CI -0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage

  11. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    2017-07-01

    In a previous phase 3 study in patients with amyotrophic lateral sclerosis (ALS), edaravone did not show a significant difference in the Revised ALS Functional Rating Scale (ALSFRS-R) score compared with placebo. Post-hoc analysis of these data revealed that patients in an early stage with definite or probable diagnosis of ALS, defined by the revised El Escorial criteria, who met a select set of inclusion criteria showed a greater magnitude of effect than did the full study population. We aimed to substantiate this post-hoc result and assess safety and efficacy of edaravone in a phase 3 trial that focused on patients with early stage ALS who met the post-hoc analysis inclusion criteria. In this phase 3, randomised, double-blind, parallel-group study, patients aged 20-75 years with ALS of grade 1 or 2 in the Japan ALS Severity Classification, scores of at least 2 points on all 12 items of ALSFRS-R, forced vital capacity of 80% or more, definite or probable ALS according to the revised El Escorial criteria, and disease duration of 2 years or less were recruited from 31 hospitals in Japan. Eligible patients also had a decrease of 1-4 points in the ALSFRS-R score during a 12-week observation period before randomisation. Patients meeting all criteria were then randomly assigned 1:1 to receive 60 mg intravenous edaravone or intravenous saline placebo for 6 cycles (4 weeks per cycle with 2 weeks on, 2 weeks off) for a total treatment duration of 24 weeks. In cycle 1, the study drug or placebo was administered once per day for 14 days within a 14 day period, followed by the drug-free period. In cycle 2 and thereafter, the study drug or placebo was administered for 10 days within a 14 day period, followed by a 2 week drug-free period. Participants and investigators, including those assessing outcomes, were masked to treatment allocation. The primary efficacy outcome was the change in ALSFRS-R score from the baseline to 24 weeks (or at discontinuation if this was after the

  12. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

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    Holman, Rury R; Coleman, Ruth L; Chan, Juliana C N; Chiasson, Jean-Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J; Tendera, Michal; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu

    2017-11-01

    The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009

  13. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

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    Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

    2015-09-01

    Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355

  14. Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

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    Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

    2018-05-03

    Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. The mean depression change was - 0.66 (95% confidence interval - 2.27 to 0.94) in the active group (n = 80) and - 3.30 (- 4.68 to -1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55-4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by - 1.11 (- 2.16 to - 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (- 0.11 to 6.19), p = 0

  15. Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo.

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    Burgess, Ian F; Brunton, Elizabeth R; French, Rebecca; Burgess, Nazma A; Lee, Peter N

    2014-05-30

    To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations. Randomised, double-blind, cross-over, community study in Cambridgeshire, UK. 63 male and female schoolchildren aged 4-16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated. Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray. The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use. Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days. Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly. ISRCTN09524995. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Patel Jeetesh V

    2011-12-01

    Full Text Available Abstract Background Coronary heart disease (CHD is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk. Methods/Design The Diabetes Health, Residence & Metabolism in Asians (DHRMA study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI supply of chapatti (bread, stone ground, high protein wheat flour and white basmati rice (high bran, unpolished or commercially available (leading brand versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner. Discussion It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive for South Asian ethnic communities. Trial registration Current Controlled Trials ISRCTN02839188

  17. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

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    Judit Villar-García

    Full Text Available Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP and systemic inflammation (IL-6 in 44 HIV virologically suppressed patients, half of whom (n = 22 had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load. The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14 and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria. Thus, in this work, we propose

  18. Daily co-trimoxazole prophylaxis to prevent mortality in children with complicated severe acute malnutrition: a multicentre, double-blind, randomised placebo-controlled trial.

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    Berkley, James A; Ngari, Moses; Thitiri, Johnstone; Mwalekwa, Laura; Timbwa, Molline; Hamid, Fauzat; Ali, Rehema; Shangala, Jimmy; Mturi, Neema; Jones, Kelsey D J; Alphan, Hassan; Mutai, Beatrice; Bandika, Victor; Hemed, Twahir; Awuondo, Ken; Morpeth, Susan; Kariuki, Samuel; Fegan, Gregory

    2016-07-01

    Children with complicated severe acute malnutrition (SAM) have a greatly increased risk of mortality from infections while in hospital and after discharge. In HIV-infected children, mortality and admission to hospital are prevented by daily co-trimoxazole prophylaxis, despite locally reported bacterial resistance to co-trimoxazole. We aimed to assess the efficacy of daily co-trimoxazole prophylaxis on survival in children without HIV being treated for complicated SAM. We did a multicentre, double-blind, randomised, placebo-controlled study in four hospitals in Kenya (two rural hospitals in Kilifi and Malindi, and two urban hospitals in Mombasa and Nairobi) with children aged 60 days to 59 months without HIV admitted to hospital and diagnosed with SAM. We randomly assigned eligible participants (1:1) to 6 months of either daily oral co-trimoxazole prophylaxis (given as water-dispersible tablets; 120 mg per day for age malnutrition (kwashiorkor), and 1221 (69%) were stunted (length-for-age Z score child-years of observation, 122 (14%) of 887 children in the co-trimoxazole group died, compared with 135 (15%) of 891 in the placebo group (unadjusted hazard ratio [HR] 0·90, 95% CI 0·71-1·16, p=0·429; 16·0 vs 17·7 events per 100 child-years observed (CYO); difference -1·7 events per 100 CYO, 95% CI -5·8 to 2·4]). In the first 6 months of the study (while participants received study medication), 63 suspected grade 3 or 4 associated adverse events were recorded among 57 (3%) children; 31 (2%) in the co-trimoxazole group and 32 (2%) in the placebo group (incidence rate ratio 0·98, 95% CI 0·58-1·65). The most common adverse events of these grades were urticarial rash (grade 3, equally common in both groups), neutropenia (grade 4, more common in the co-trimoxazole group), and anaemia (both grades equally common in both groups). One child in the placebo group had fatal toxic epidermal necrolysis with concurrent Pseudomonas aeruginosa bacteraemia. Daily co

  19. The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James H; Chang, J Judy; Audsley, Jennifer; Rhodes, Ajantha; Tennakoon, Surekha; Dantanarayana, Ashanti; Spelman, Tim; Schmidt, Tina; Kent, Stephen J; Morcilla, Vincent; Palmer, Sarah; Elliott, Julian H; Lewin, Sharon R

    2018-04-06

    Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per mL at screening and two CD4 counts higher than 350 cells per μL in the previous 24 months including screening. Participants were randomly assigned (1:1) to receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The primary outcome was the change from baseline in frequency of 2-long terminal repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is registered with ClinicalTrials.gov, number NCT02500446. Between Sept 21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or placebo group (n=19). All enrolled participants completed the study procedures and no individuals were lost to follow up. All participants were on suppressive ART with 12% receiving protease inhibitors and the others non-nucleoside reverse transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7 was -0·17 (IQR -0·90 to 0·90) in the dolutegravir group and -0·26 (-1·00 to 1·17) in the placebo group (p=0·17). The addition of dolutegravir to pre-existing ART regimens was safe and

  20. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Hirayama, S; Terasawa, K; Rabeler, R; Hirayama, T; Inoue, T; Tatsumi, Y; Purpura, M; Jäger, R

    2014-04-01

    Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). PS supplementation resulted in significant improvements in: (i) ADHD (P short-term auditory memory (P short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  1. Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Lin, Chun-Yuan; Liang, Sun-Yuan; Chang, Yue-Cune; Ting, Shuo-Yen; Kao, Ching-Ling; Wu, Yu-Hsin; Tsai, Guochuan E; Lane, Hsien-Yuan

    2017-08-01

    Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.

  2. A Randomised, Double-Blind, Placebo-Controlled Trial of Actovegin in Patients with Post-Stroke Cognitive Impairment: ARTEMIDA Study Design

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    Alla Guekht

    2013-12-01

    Full Text Available Background: No drug treatment to date has shown convincing clinical evidence of restoring cognitive function or preventing further decline after stroke. The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI and will explore whether Actovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment. Design: ARTEMIDA is a 12-month, multicentre trial in patients (planned a total of 500, now recruited with cognitive impairment following ischaemic stroke. The study consists of a baseline screening (≤7 days after stroke, after which eligible patients are randomised to Actovegin (2,000 mg/day for up to 20 intravenous infusions followed by 1,200 mg/day orally or placebo for a 6-month double-blind treatment period. Patients will be followed up for a further 6 months, during which time they will be treated in accordance with standard clinical practice. The primary study endpoint is change from baseline in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version. Secondary outcomes include: Montreal Cognitive Assessment; dementia diagnosis (ICD-10; National Institutes of Health Stroke Scale; Barthel Index; EQ-5D; Beck Depression Inventory, version II, and safety. Conclusion: There is a clear need for effective treatments for PSCI. ARTEMIDA should provide important insights into the use of a novel drug therapy for PSCI.

  3. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 1; referees: 2 approved

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    Rebeccah Slater

    2016-11-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  4. A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol.

    Science.gov (United States)

    Fernando, Shavi; Osianlis, Tiki; Vollenhoven, Beverley; Wallace, Euan; Rombauts, Luk

    2014-09-01

    High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3-4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose-response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2'-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. ACTRN12613001317785. Published by the BMJ Publishing Group Limited. For permission to use (where

  5. Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

    Science.gov (United States)

    Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

    2016-11-29

    Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  6. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

    2014-06-21

    Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; protavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5

  7. [Treating pain after dental surgery: a randomised, controlled, double-blind trial to assess a new formulation of paracetamol, opium powder and caffeine versus tramadol or placebo].

    Science.gov (United States)

    Borel, Jean-François; Deschaumes, Christophe; Devoize, Laurent; Huard, Cédric; Orliaguet, Thierry; Dubray, Claude; Baudet-Pommel, Martine; Dallel, Radhouane

    2010-05-01

    The aim of this study was to evaluate the analgesic efficacy and the safety of the association, paracetamol, opium prepared and caffeine, in two different dosages as compared to the conventional analgesic tramadol hydrochloride, on acute postoperative dental pain. We conducted a randomised, double-blind, multicentre, parallel-group clinical trial to test the efficacy and safety of single doses of two associations; paracetamol 500 mg, caffeine 50mg, opium prepared 25, and paracetamol 500 mg, caffeine 50mg, opium prepared 50mg, as compared to tramadol hydrochloride 100mg (called hereafter tramadol 100), and placebo, in the control of postoperative pain following the removal of 2 ipsilateral impacted third molars. The primary efficacy criterion was the sum of pain intensity differences as assessed every 30 minutes within 3 hours after the baseline assessment and administration of study treatment (SPID(0-3h)). Of the 232 randomised patients, 228 (98%) completed the study. Analysis of the primary efficacy criterion (SPID(0-3h)) established: (i) the superiority of the 3 active study treatments vs. placebo (popium 25mg, and paracetamol, caffeine, and opium 50mg vs. tramadol. Besides, both formulations of paracetamol, caffeine, and opium showed: (i) a faster onset of analgesic effect as compared to tramadol 100; (ii) a significantly stronger analgesic efficacy than tramadol 100, as measured 1 hour after the treatment intake; this superiority lasted all over the study duration for paracetamol, caffeine, and opium 50mg but not for paracetamol, caffeine, and opium 25mg. No unexpected safety concerns occurred, the two formulations of paracetamol, caffeine, and opium showed a good safety profile especially with paracetamol, caffeine, and opium 25mg as compared to tramadol. This study evidenced the non-inferiority of the paracetamol, caffeine, and opium 25mg or 50mg vs. tramadol 100, and even though the strengths of the tested formulations were higher than that of the 2009

  8. The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial--study protocol.

    Science.gov (United States)

    Lee, Dong-Hyo; Seo, Eun-Sung; Hong, Jin-Tae; Lee, Gang-Tai; You, Young-Kyoung; Lee, Kun-Kook; Jo, Ga-Won; Kim, Nam-Kwen

    2013-11-25

    Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition.This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ health-related quality of life

  9. The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial- study protocol

    Science.gov (United States)

    2013-01-01

    Background Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition. This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. Methods/Designs This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. Discussion This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ

  10. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

    Science.gov (United States)

    Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

    2015-01-01

    Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

  11. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.

    Science.gov (United States)

    Thiele, Elizabeth A; Marsh, Eric D; French, Jacqueline A; Mazurkiewicz-Beldzinska, Maria; Benbadis, Selim R; Joshi, Charuta; Lyons, Paul D; Taylor, Adam; Roberts, Claire; Sommerville, Kenneth

    2018-03-17

    Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients. In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2-55 years) had Lennox-Gastaut syndrome, including a history of slow (caregivers, investigators, and individuals assessing data were masked to group assignment. The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period, analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data. All randomly assigned patients were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02224690. Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85). 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR -69·6 to -1·9) in the cannibidiol group and 21·8% (IQR -45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was -17·21 (95% CI -30·32 to -4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of

  12. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.

    Science.gov (United States)

    Huttner, Angela; Dayer, Julie-Anne; Yerly, Sabine; Combescure, Christophe; Auderset, Floriane; Desmeules, Jules; Eickmann, Markus; Finckh, Axel; Goncalves, Ana Rita; Hooper, Jay W; Kaya, Gürkan; Krähling, Verena; Kwilas, Steve; Lemaître, Barbara; Matthey, Alain; Silvera, Peter; Becker, Stephan; Fast, Patricia E; Moorthy, Vasee; Kieny, Marie Paule; Kaiser, Laurent; Siegrist, Claire-Anne

    2015-10-01

    Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the Zaire Ebola virus glycoprotein (rVSV-ZEBOV; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or 5 × 10(7) pfu (n=16) of rVSV-ZEBOV (high-dose vaccinees) or placebo (n=8) before a safety-driven study hold. The Geneva rVSV-ZEBOV study, an investigator-initiated phase 1/2, dose-finding, placebo-controlled, double-blind trial conducted at the University Hospitals of Geneva, Switzerland, enrolled non-pregnant, immunocompetent, and otherwise healthy adults aged 18-65 years. Participants from the low-dose group with no plans to deploy to Ebola-aff5cted regions (non-deployable) were randomised 9:1 in a double-blind fashion using randomly permuted blocks of varying sizes to a single injection of 3 × 10(5) pfu or placebo, whereas deployable participants received single-injection 3 × 10(5) pfu open-label. Primary safety and immunogenicity outcomes were the incidence of adverse events within 14 days of vaccination and day-28 antibody titres, respectively, analysed by intention to treat. After viral oligoarthritis was observed in 11 of the first 51 vaccinees (22%) receiving 10(7) or 5 × 10(7) pfu, 56 participants were given a lower dose (3 × 10(5) pfu, n=51) or placebo (n=5) to assess the effect of dose reduction on safety and immunogenicity. This trial is ongoing with a follow-up period of 12 months; all reported results are from interim databases. This study is registered with ClinicalTrials.gov, number NCT02287480. Between Jan 5 and Jan 26, 2015, 43 non-deployable participants received low-dose rVSV-ZEBOV (3 × 10(5) pfu) or placebo in a

  13. Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial).

    Science.gov (United States)

    Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup; Poulsen, Jakob Lykke; Dahan, Albert; Wilder-Smith, Oliver; Madzak, Adnan; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr

    2015-03-10

    Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of the N-methyl-D-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. 40 patients with CP will be enrolled. Patients are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8 weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP. The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences

  14. Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

    Science.gov (United States)

    Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

    1998-01-01

    OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition

  15. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Poulsen, L K; Jacobi, H H

    2002-01-01

    BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North Americ...

  16. Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial

    NARCIS (Netherlands)

    Tasma, M L; Louwerse, M D; Hehenkamp, W J; Geomini, P M; Bongers, M Y; Veersema, S; van Kesteren, P J; Tromp, E; Huirne, J A; Graziosi, G C

    OBJECTIVE: To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women. DESIGN: Randomised multicentre double-blind placebo controlled trial. SETTING: Two Dutch teaching hospitals and one Dutch university medical

  17. A Placebo-Controlled, Blinded and Randomised Study on the Effects of Recombinant Human Thyrotropin on Quality of Life in the Treatment of Thyroid Cancer

    DEFF Research Database (Denmark)

    Nygaard, Birte; Bastholt, Lars; Bennedbæk, Finn Noe

    2013-01-01

    BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. OBJECTIVE: To compare QOL...... in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. STUDY DESIGN: Double-blind, randomised cross-over. PATIENTS: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy...

  18. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Rouphael, Nadine G; Paine, Michele; Mosley, Regina; Henry, Sebastien; McAllister, Devin V; Kalluri, Haripriya; Pewin, Winston; Frew, Paula M; Yu, Tianwei; Thornburg, Natalie J; Kabbani, Sarah; Lai, Lilin; Vassilieva, Elena V; Skountzou, Ioanna; Compans, Richard W; Mulligan, Mark J; Prausnitz, Mark R

    2017-08-12

    Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat

  19. A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age.

    Science.gov (United States)

    Perry, N S L; Menzies, R; Hodgson, F; Wedgewood, P; Howes, M-J R; Brooker, H J; Wesnes, K A; Perry, E K

    2018-01-15

    To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Short and long-term effects of irbesartan on intradialytic central haemodynamics: A randomised double-blind placebo-controlled one-year intervention trial (the SAFIR study)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

    2014-01-01

    ), stroke volume (SV), central blood volume (CBV), total peripheral resistance (TPR), mean arterial BP (MAP), and heart rate (HR) were measured within the first (HDSTART) and last (HDEND) 30 minutes during HD using the Transonic saline dilution technique. Results Eighty-two patients were randomised (placebo....../ARB: 41/41). Predialytic systolic BP decreased significantly, but similarly in both groups during the study period. The total number of IDH episodes was (placebo/ARB) 22/25 (P=0.7). Mean HDSTART and mean HDEND CO, SV, TPR, HR, and MAP were stable and similar in the two groups, whereas CBV increased...... equally and significantly over time. The mean intradialytic haemodynamic response showed decreased CO, SV, MAP, and CBV, whereas HR increased from HDSTART to HDEND. TPR did not change significantly. Overall, this pattern remained stable over time in both groups and there was no significant impact of ARB...

  1. EFFECTS OF ANGIOTENSIN II BLOCKADE WITH IRBESARTAN ON INFLAMMATORY MARKERS IN HAEMODIALYSIS PATIENTS: A RANDOMISED DOUBLE BLIND PLACEBO CONTROLLED ONE-YEAR FOLLOW-UP TRIAL (SAFIR STUDY)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Nielsen, Claus H.

    as factors using Stata/IC 12.1. Results Eighty-two patients were randomised (placebo/irbesartan: 41/41) and 56 completed one year of treatment. The groups (placebo/irbesartan) were comparable at baseline (mean±SD): Males 26(63%)/30(73%); age 62±14/61±16 years; systolic blood pressure (BP) 145±19/148±21 mm......Hg; HD vintage 168±95/171±93 days; HD time 10±2/11±3 hr/week; urine output 1.3±0.7/1.5±0.8 L/24 h; glomerular filtration rate 4.8/5.7 mL/min/1.73m2. Predialysis systolic BP decreased to the same extent in the irbesartan (–10 mm Hg) and in the placebo arm (–8 mm Hg). Use of additional antihypertensive......(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-13.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between patients receiving placebo, and irbesartan treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P...

  2. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I

    2014-01-01

    BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel...... chemotherapy. METHODS: We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8 Gy in one...... fraction) followed by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly...

  3. The Effect of Ginger (Zingiber officinalis and Artichoke (Cynara cardunculus Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Attilio Giacosa

    2015-01-01

    Full Text Available Objective. Functional dyspepsia (FD is a frequent clinical finding in western world. The aim of this study is to compare the efficacy of a ginger and artichoke supplementation versus placebo in the treatment of FD. Methods. A prospective multicentre, double blind, randomized, placebo controlled, parallel-group comparison of the supplement and placebo over a period of 4 weeks was performed. Two capsules/day were supplied (before lunch and dinner to 126 FD patients (supplementation/placebo: 65/61. Results. After 14 days of treatment, only supplementation group (SG showed a significant amelioration (SG: αS=+1.195 MCA score units (u, P=0.017; placebo: αP=+0.347 u, P=0.513. The intercept (α resulted to be significantly higher in SG than in placebo (αS-αP=+0.848 u, P<0.001. At the end of the study, the advantage of SG versus placebo persists without variation (βS-βP=+0.077 u, P=0.542. In SG, a significant advantage is observed for nausea (βS-βP=-0.398 u, P<0.001, epigastric fullness (βS-βP=-0.241, P<0.001, epigastric pain (βS-βP=-0.173 u, P=0.002, and bloating (βS-βP=-0.167 u, P=0.017. Conclusions. The association between ginger and artichoke leaf extracts appears safe and efficacious in the treatment of FD and could represent a promising treatment for this disease.

  4. A double-blind randomised, placebo-controlled trial evaluating the influence of oral long-acting muscle relaxant (Mebeverine MR), and insufflation with CO{sub 2} on pain associated with barium enema

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, A.S.; Chapman, A.H.; Wilson, D.; Culpan, A.G. [Department of Radiology, St. James' s University Hospital, Beckett Street, LS9 7TF, Leeds (United Kingdom)

    2003-07-01

    Previous investigators have shown significant benefit using CO{sub 2} for bowel insufflation. Others have suggested that the long-acting smooth muscle relaxant, Mebeverine, may be of benefit. We subjected this to a randomised double-blind trial. A total of 181 outpatients were randomised to receive either Mebeverine or placebo as pre-medication, and either air or CO{sub 2} for bowel insufflation, thus creating four treatment groups. Visual-analogue lines were used to record pain scores before, during, and up to 8 h following the enema. All groups showed increased pain scores during the enema, with peak pain scores at the end of the examination, falling to baseline scores by 8 h. Patients receiving the combination of C0{sub 2} and placebo had significantly lower pain scores at 1 and 4 h (P=0.00 and P=0.014, respectively; Kruskal-Wallis test) compared with all other groups. Having Mebeverine as a pre-medication did not significantly lower pain scores compared with placebo, and decreased the amount of benefit received from the CO{sub 2}. We confirm that CO{sub 2} is of benefit in decreasing pain during barium enema, and we recommend its routine use to improve the comfort of patients. Mebeverine is not of benefit, and its use as a pre-medication for enemas is not recommended. (orig.)

  5. Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

    2014-06-19

    We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922.

  6. Dietary Supplementation with a Superoxide Dismutase-Melon Concentrate Reduces Stress, Physical and Mental Fatigue in Healthy People: A Randomised, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2014-06-01

    Full Text Available Background: We aimed to investigate effects of superoxide dismutase (SOD-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. Methods: A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32 and placebo (n = 29 for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. Results: The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. Conclusion: SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. Trial registration: trial approved by the ethical committee of Poitiers (France, and the ClinicalTrials.gov Identifier is NCT01767922.

  7. Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study

    Science.gov (United States)

    Marteau, P; Crand, J; Foucault, M; Rambaud, J

    1998-01-01

    Background—Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage. 
Aim—The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied. 
Methods—Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n=48) or placebo (n=47). In the case of a relapse, the patients received one suppository/day. 
Results—It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0-90 days (19% v 38%, p=0.035), 0-180 days (29% v 54%, p=0.017), 0-270 days (38% v 60%, p=0.031), and 0-365 days (48% v 62%, p=0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p=0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p=0.001). Tolerance was good. 
Conclusion—Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed. 

 Keywords: inflammatory bowel disease; mesalazine; 5-aminosalicylic acid; topical treatments; proctitis PMID:9536943

  8. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial.

    Science.gov (United States)

    Giannetti, B M; Staiger, C; Bulitta, M; Predel, H-G

    2010-07-01

    The objective was to show the superiority of comfrey root extract ointment to placebo ointment in patients with acute upper or lower back pain. The study was conducted as a double-blind, multicentre, randomised clinical trial with parallel group design over a period of 5 days (SD 1). The patients (n = 120, mean age 36.9 years) were treated with verum or placebo ointment three times a day, 4 g ointment per application. The trial included four visits. The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardised movement values at visits 1 to 4. The secondary efficacy variables were back pain at rest using assessment by the patient on VAS, pressure algometry (pain-time curve; AUC over 5 days), global assessment of efficacy by the patient and the investigator, consumption of analgesic medication and functional impairment measured using the Oswestry disability index. There was a significant treatment difference between comfrey extract and placebo regarding the primary variable. In the course of the trial the pain intensity on active standardised movement decreased on average (median) approximately 95.2% in the verum group and 37.8% in the placebo group. The results of this clinical trial were clear-cut and consistent across all primary and secondary efficacy variables. Comfrey root extract showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 h) was also witnessed.

  9. Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

    2001-01-01

    Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the

  10. Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Osborne Richard

    2007-09-01

    Full Text Available Abstract Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA, there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259.

  11. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

    2016-03-01

    Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70

  12. A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

    Science.gov (United States)

    Dean, Olivia M; Gray, Kylie M; Villagonzalo, Kristi-Ann; Dodd, Seetal; Mohebbi, Mohammadreza; Vick, Tanya; Tonge, Bruce J; Berk, Michael

    2017-03-01

    Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

  13. Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    Directory of Open Access Journals (Sweden)

    David J. White

    2016-01-01

    Full Text Available l-theanine (γ-glutamylethylamide is an amino acid found primarily in the green tea plant. This study explored the effects of an l-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG. Thirty-four healthy adults aged 18–40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the l-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of l-theanine.

  14. Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study.

    Science.gov (United States)

    Jones, David; Boudes, Pol F; Swain, Mark G; Bowlus, Christopher L; Galambos, Michael R; Bacon, Bruce R; Doerffel, Yvonne; Gitlin, Norman; Gordon, Stuart C; Odin, Joseph A; Sheridan, David; Wörns, Markus-Alexander; Clark, Virginia; Corless, Linsey; Hartmann, Heinz; Jonas, Mark E; Kremer, Andreas E; Mells, George F; Buggisch, Peter; Freilich, Bradley L; Levy, Cynthia; Vierling, John M; Bernstein, David E; Hartleb, Marek; Janczewska, Ewa; Rochling, Fedja; Shah, Hemant; Shiffman, Mitchell L; Smith, John H; Choi, Yun-Jung; Steinberg, Alexandra; Varga, Monika; Chera, Harinder; Martin, Robert; McWherter, Charles A; Hirschfield, Gideon M

    2017-10-01

    Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the

  15. Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

    Science.gov (United States)

    Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

    2014-03-01

    Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy

  16. Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

    Science.gov (United States)

    López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

    2018-06-01

    Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in

  17. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured

  18. Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease.

    Science.gov (United States)

    Thomas, E; Wade, A; Crawford, G; Jenner, B; Levinson, N; Wilkinson, J

    2014-03-01

    The alginate-antacid, Gaviscon Double Action (Gaviscon DA; Reckitt Benckiser, Slough, UK) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction. The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design. A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease (GERD) patients. A randomised, double-blind, parallel group study was performed in 110 patients with symptoms of GERD. Patients received Gaviscon DA or placebo tablets for 7 consecutive days. The primary endpoint compared the change in overall Reflux Disease Questionnaire (RDQ) symptom score (combined heartburn/regurgitation/dyspepsia). Secondary endpoints assessed individual dimensions, GERD dimension (heartburn and regurgitation) and overall treatment evaluation (OTE). There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group (Least Squares Mean difference -0.55; P = 0.0033), and for each of the dimensions independently. Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [mean (standard deviation) OTE 4.1 (2.44) vs. 1.9 (3.34); P = 0.0005]. No differences in the incidence of adverse events were observed between treatment groups. Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance. Larger scale clinical investigations of medications targeting the acid pocket are warranted. (EudraCT, 2012-002188-84). © 2014 John Wiley & Sons Ltd.

  19. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

    Science.gov (United States)

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Iwasaki, Manabu; Ishikura, Hiroaki; Saeki, Satoshi; Kaneko, Yuichiro

    2016-01-01

    Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results. PMID:26672064

  20. Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Takei, Koji; Takahashi, Fumihiro; Liu, Shawn; Tsuda, Kikumi; Palumbo, Joseph

    2017-10-01

    Post-hoc analyses of the ALS Functional Rating Scale-Revised (ALSFRS-R) score data, the primary endpoint in the 24-week double-blind placebo-controlled study of edaravone (MCI186-19, NCT01492686), were performed to confirm statistical robustness of the result. The previously reported original analysis had used a last observation carried forward (LOCF) method and also excluded patients with fewer than three completed treatment cycles. The post-hoc sensitivity analyses used different statistical methods as follows: 1) including all patients regardless of treatment cycles received (ALL LOCF); 2) a mixed model for repeated measurements (MMRM) analysis; and 3) the Combined Assessment of Function and Survival (CAFS) endpoint. Findings were consistent with the original primary analysis in showing superiority of edaravone over placebo. We also investigated the distribution of change in ALSFRS-R total score across all patients in the study as well as which ALSFRS-R items and domains may have contributed to the overall efficacy findings. The distribution of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF) shifted in favour of edaravone compared to placebo. Edaravone was descriptively favoured for each ALSFRS-R item and each of the four ALSFRS-R domains at the end of cycle 6 (ALL LOCF), suggesting a generalised effect of edaravone in slowing functional decline across all anatomical regions. The effect of edaravone appeared to be similar in patients with bulbar onset and limb onset. Together, these observations would be consistent with its putative neuroprotective effects against the development of oxidative damage unspecific to anatomical regions.

  1. A randomised, double-blind, placebo-controlled trial of nightly sildenafil citrate to preserve erectile function after radiation treatment for prostate cancer

    International Nuclear Information System (INIS)

    Ilic, Dragan; Hindson, Ben; Duchesne, Gillian; Millar, Jeremy L.

    2013-01-01

    Erectile dysfunction (ED) is a common adverse event associated with treatment for prostate cancer. This study aimed to identify whether early, regular use of sildenafil after radiation treatment for prostate cancer is effective at reducing the rate of ED at 2 years. A randomised controlled trial with 27 men planned for radiation treatment for localised prostate cancer recruited from a single radiotherapy centre in Australia. Men were randomised to receive daily sildenafil, or a placebo tablet, for 6 months. The primary end-point was erectile function, as measured by the International Index of Erectile Function (IIEF) score, at 2-year follow-up. The abridged IIEF-5 survey was also used during the treatment period, and could be derived from the full IIEF at other time-points. Two-sided Student's t-tests and Mann–Whitney U-tests were used for the analysis of continuous outcomes, with Fisher's exact test for dichotomous outcomes. No difference was seen at 2 years in the primary end-point, and IIEF scores did not differ significantly between groups during the study. Men in the sildenafil group exhibited significantly better IIEF-5 scores at 4 weeks (P=0.02) and 6 months (P=0.02). There was no difference in erectile function scores between the two groups throughout the treatment period. No significant difference in adverse events was identified between the two groups. There was no evidence from this trial that sildenafil provides long-term erectile function for patients while on medication. Regular use of sildenafil may improve short-term sexual function for patients while on medication. Larger trials are required to examine the effectiveness of implementing sildenafil for prostate cancer patients undergoing radiation treatment.

  2. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study

    Directory of Open Access Journals (Sweden)

    Madhuri S Kurdi

    2016-01-01

    Full Text Available Background and Aims: Melatonin (MT, a naturally occurring pituitary hormone has a sleep promoting effect. There are very few studies on pre-operative oral MT (0.2-0.5 mg/kg in children. We planned a study to assess the efficacy of oral MT in two doses and compare it with oral midazolam and placebo for pre-operative anxiolysis, sedation, maintenance of cognition and psychomotor skills, parental separation behaviour and venepuncture compliance. Methods: This prospective double-blind randomised study was conducted after ethical committee approval on 100 children aged 5-15 years, American Society of Anaesthesiologists physical status I and II undergoing elective surgery at our hospital from January 1, 2014, to December 31, 2014. Mentally disordered children were excluded from the study. They were randomised into four groups of 25 each (A, B, C, D to receive either oral MT 0.5 mg/kg or 0.75 mg/kg or oral midazolam 0.5 mg/kg or placebo 45-60 min, respectively, before induction. The child′s anxiety, cognition and psychomotor function before and after pre-medication, behaviour during the parental separation and venepuncture were appropriately scored. Kruskal-Wallis analysis of variance for intergroup and Wilcoxon matched pairs tests for intragroup comparisons of data were applied. Results: The four groups were comparable regarding mean age, weight and sex. The anxiety score reductions in the three groups when compared to placebo were statistically significant. Children receiving MT 0.75 mg/kg had maximum anxiolysis and venepuncture compliance (P < 0.05. Cognition was decreased with maximum sedation, successful parental separation and psychomotor impairment in the midazolam group (P < 0.05. Conclusion: Oral MT (0.5 mg/kg and 0.75 mg/kg in children decreases pre-operative anxiety without impairing cognitive and psychomotor functions, the 0.75 mg/kg dose being most effective.

  3. Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Richmond, Peter C; Marshall, Helen S; Nissen, Michael D; Jiang, Qin; Jansen, Kathrin U; Garcés-Sánchez, Maria; Martinón-Torres, Federico; Beeslaar, Johannes; Szenborn, Leszek; Wysocki, Jacek; Eiden, Joseph; Harris, Shannon L; Jones, Thomas R; Perez, John L

    2012-08-01

    Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease, but a broadly protective vaccine is not currently licensed. A bivalent recombinant factor H-binding protein vaccine (recombinant lipoprotein 2086) has been developed to provide broad coverage against diverse invasive meningococcus serogroup B strains. Our aim was to test the immune response of this vaccine. This randomised, placebo-controlled trial enrolled healthy adolescents from 25 sites in Australia, Poland, and Spain. Exclusion criteria were previous invasive meningococcal disease or serogroup B vaccination, previous adverse reaction or known hypersensitivity to the vaccine, any significant comorbidities, and immunosuppressive therapy or receipt of blood products in the past 6 months. Participants were randomly assigned with a computerised block randomisation scheme to receive ascending doses of vaccine (60, 120, or 200 μg) or placebo at 0, 2, and 6 months. Principal investigators, participants and their guardians, and laboratory personnel were masked to the allocation; dispensing staff were not. Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The co-primary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17) analysed by the Clopper-Pearson method. Local and systemic reactions and adverse events were recorded. The study is registered at ClinicalTrials.gov, number NCT00808028. 539 participants were enrolled and 511 received all three study vaccinations--116 in the placebo group, 21 in the 60 μg group, 191 in the 120 μg group, and 183 in the 200 μg group. The proportion of participants responding with an hSBA titre equal to or greater than the lower limit of quantitation of the hSBA assays (reciprcocal titres of 7 to 18, depending on test strain) was similar for the two largest doses and ranged from 75·6 to 100·0% for the 120 μg dose and 67·9 to

  4. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.

    Science.gov (United States)

    Howard, James F; Utsugisawa, Kimiaki; Benatar, Michael; Murai, Hiroyuki; Barohn, Richard J; Illa, Isabel; Jacob, Saiju; Vissing, John; Burns, Ted M; Kissel, John T; Muppidi, Srikanth; Nowak, Richard J; O'Brien, Fanny; Wang, Jing-Jing; Mantegazza, Renato

    2017-12-01

    Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators

  5. A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Palmer, Melissa; Jennings, Lee; Silberg, Debra G; Bliss, Caleb; Martin, Patrick

    2018-03-16

    Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990

  6. A randomised, double-blind, placebo controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread in healthy volunteers.

    Science.gov (United States)

    Walton, Gemma E; Lu, Congyi; Trogh, Isabel; Arnaut, Filip; Gibson, Glenn R

    2012-06-01

    Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS) at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA) levels in saliva were also measured. Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated.

  7. A randomised, double-blind, placebo controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Walton Gemma E

    2012-06-01

    Full Text Available Abstract Background Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. Methods A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA levels in saliva were also measured. Results Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. Conclusions AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated.

  8. Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

    Directory of Open Access Journals (Sweden)

    Jackson Andrew L

    2009-02-01

    Full Text Available Abstract Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH. Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A, and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%. Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50 and 1740 (S.E. 291 in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237 and 1126 (S.E. 182 in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes. Trial Registration Current controlled trials ISRCTN44215995.

  9. Reduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524®) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Kean, James D; Sarris, Jerome; Scholey, Andrew; Silberstein, Richard; Downey, Luke A; Stough, Con

    2017-02-01

    This study investigated the effects of a marine oil extract (PCSO-524®) on inattention, hyperactivity, mood and cognition in children and adolescents. PCSO-524® is a standardised lipid extract of the New Zealand green-lipped mussel and is an inflammatory modulator that inhibits the 5'-lipoxygenase and cyclooxygenase pathways and decreases concentrations of the pro-inflammatory arachidonic acid (AA). PCSO-524® or a matched placebo was administered for 14 weeks to 144 participants (123 males/21 females; mean age 8.7 years) with high hyperactivity and inattention in a randomised, double-blind, placebo-controlled study. The primary outcome was the Conners Parent Rating Scale assessing parental reports of behavioural problems. Secondary outcomes assessed changes in cognition and mood. The results of the present study did not support the hypothesis that PCSO-524® improves parental reports of hyperactivity, inattention and impulsivity in children ages 6 to 14 years over placebo. Repeated measures ANOVA on post hoc subsample analysis indicated significant improvements in hyperactivity (p = 0.04), attention (p = 0.02), learning (p = 0.05) and probability of ADHD (p = 0.04) with a medium to large average effect size (d = 0.65) in those children who did not meet criteria for combined hyperactivity and inattention. Furthermore, significant improvements in the PCSO-524® group were indicated in a whole sample repeated measures ANCOVA on recognition memory between baseline and week 8 over placebo (p = 0.02, d = 0.56); this difference was not sustained at week 14. The results presented indicate that PCSO-524® may be beneficial in reducing levels of hyperactivity and inattention in a population of children with clinical and subclinical symptoms of ADHD.

  10. Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial.

    Science.gov (United States)

    Pleguezuelos, Olga; Robinson, Stuart; Stoloff, Gregory A; Caparrós-Wanderley, Wilson

    2012-06-29

    Current Influenza vaccines elicit antibody mediated prophylactic immunity targeted to viral capsid antigens. Despite their global use these vaccines must be administered yearly to the population, cannot be manufactured until the circulating viral strain(s) have been identified and have limited efficacy. A need remains for Influenza vaccines addressing these issues and here we report the results of a Phase Ib trial of a novel synthetic Influenza vaccine (FLU-v) targeting T cell responses to NP, M1 and M2. Forty-eight healthy males aged 18-40 were recruited for this single-centre, randomised, double blind study. Volunteers received one single low (250 μg) or high (500 μg) dose of FLU-v, either alone or adjuvanted. Safety, tolerability and basic immunogenicity (IgG and IFN-γ responses) parameters were assessed pre-vaccination and for 21 days post-vaccination. FLU-v was found to be safe and well tolerated with no vaccine associated severe adverse events. Dose-dependent IFN-γ responses >2-fold the pre-vaccination level were detected in 80% and 100% of volunteers receiving, respectively, the low and high dose adjuvanted FLU-v formulations. No formulation tested induced any significant FLU-v antibody response. FLU-v is safe and induces a vaccine-specific cellular immunity. Cellular immune responses are historically known to control and mitigate infection and illness during natural infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

    Science.gov (United States)

    Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

    2018-01-01

    Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (Pgut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

  12. The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients - protocol for a double-blind, placebo-controlled randomised trial.

    Science.gov (United States)

    Dogar, Omara; Barua, Deepa; Boeckmann, Melanie; Elsey, Helen; Fatima, Razia; Gabe, Rhian; Huque, Rumana; Keding, Ada; Khan, Amina; Kotz, Daniel; Kralikova, Eva; Newell, James N; Nohavova, Iveta; Parrott, Steve; Readshaw, Anne; Renwick, Lottie; Sheikh, Aziz; Siddiqi, Kamran

    2018-04-20

    Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine - a low-cost plant-derived nicotine substitute - for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomised trial. TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. Newly diagnosed (in the last four weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n= 2,388). The primary outcome measure is biochemically verified continuous abstinence from smoking at six months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and tuberculosis (TB) outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke. This article is protected by copyright. All rights reserved.

  13. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

    Science.gov (United States)

    Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

    2017-06-01

    Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial.

    Science.gov (United States)

    Grube, B; Grünwald, J; Krug, L; Staiger, C

    2007-01-01

    This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (pcomfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.

  15. Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Catriona S Bradshaw

    Full Text Available BACKGROUND: To determine if oral metronidazole (MTZ-400 mg bid with 2% vaginal clindamycin-cream (Clind or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob reduces 6-month bacterial vaginosis (BV recurrence. METHODS: Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1:1:1 conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS = 7-10 or ≥3 Amsel's criteria and NS = 4-10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7-10 on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups. RESULTS: 450 18-50 year old females were randomized and 408 (91%, equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9% participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351. One-month BV recurrence (NS 7-10 rates were 3.6% (5/140, 6.8% (9/133 and 9.6% (13/135 in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15-1.22 and 0.75 (95% CI 0.32-1.76 in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0-32.7% with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70-1.70 and 1.03(95% CI = 0.65-1.63, respectively. No serious

  16. B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Almeida, Osvaldo P; Ford, Andrew H; Hirani, Varsha; Singh, Vash; vanBockxmeer, Frank M; McCaul, Kieran; Flicker, Leon

    2014-12-01

    Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration. To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks. Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94). B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults. Royal College of Psychiatrists.

  17. Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation.

    Science.gov (United States)

    van Bodegraven, Ad A; Bravenboer, Nathalie; Witte, Birgit I; Dijkstra, Gerard; van der Woude, C Janneke; Stokkers, Pieter C M; Russel, Maurice G; Oldenburg, Bas; Pierik, Marieke; Roos, Jan C; van Hogezand, Ruud A; Dik, Vincent K; Oostlander, Angela E; Netelenbos, J Coen; van de Langerijt, Lex; Hommes, Daniel W; Lips, Paul

    2014-09-01

    Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients. This double-blind, placebo-controlled randomised trial of risedronate with calcium and vitamin D supplementation was performed in osteopenic Crohn's disease patients. Patients were treated for 2 years with follow-up after 3 and after every 6 months. Disease characteristics and activity and bone turnover markers were assessed at all visits; dual x-ray absorptiometry was performed at baseline, 12 and 24 months; radiographs of the spine at baseline and 24 months. Of 132 consenting patients, 131 were randomised (67 placebo and 64 risedronate). Patient characteristics were similar in both groups, although the risedronate group was slightly heavier (body mass index 24.3 vs 23.0 kg/m(2)). Bone mineral density at lumbar spine increased 0.04 g/cm(2) on average in the risedronate group versus 0.01 g/cm(2) in the placebo group (p=0.007). The mean increase in total hip bone mineral density was 0.03 versus 0.01 g/cm(2), respectively (p=0.071). Fracture prevalence and incidence were similar. Change of T-scores and concentrations of bone turnover markers were consistent with a beneficial effect of risedronate when compared with placebo. The effect of risedronate was primarily demonstrated in the first 12 months of treatment. No serious unexpected suspected adverse events were observed. A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register. Published by the BMJ Publishing Group Limited. For permission to use

  18. Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Sophie Boisson

    2013-08-01

    Full Text Available Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five.We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC, an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account

  19. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Zhu, Feng-Cai; Hou, Li-Hua; Li, Jing-Xin; Wu, Shi-Po; Liu, Pei; Zhang, Gui-Rong; Hu, Yue-Mei; Meng, Fan-Yue; Xu, Jun-Jie; Tang, Rong; Zhang, Jin-Long; Wang, Wen-Juan; Duan, Lei; Chu, Kai; Liang, Qi; Hu, Jia-Lei; Luo, Li; Zhu, Tao; Wang, Jun-Zhi; Chen, Wei

    2015-06-06

    Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (pvaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; pday 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2

  20. Effect of supplementation of fermented milk drink containing probiotic Lactobacillus casei Shirota on the concentrations of aflatoxin biomarkers among employees of Universiti Putra Malaysia: a randomised, double-blind, cross-over, placebo-controlled study.

    Science.gov (United States)

    Mohd Redzwan, Sabran; Abd Mutalib, Mohd Sokhini; Wang, Jia-Sheng; Ahmad, Zuraini; Kang, Min-Su; Abdul Rahman, Nurul 'Aqilah; Nikbakht Nasrabadi, Elham; Jamaluddin, Rosita

    2016-01-14

    Human exposure to aflatoxin is through the diet, and probiotics are able to bind aflatoxin and prevent its absorption in the small intestine. This study aimed to determine the effectiveness of a fermented milk drink containing Lactobacillus casei Shirota (LcS) (probiotic drink) to prevent aflatoxin absorption and reduce serum aflatoxin B1-lysine adduct (AFB1-lys) and urinary aflatoxin M1 concentrations. The present study was a randomised, double-blind, cross-over, placebo-controlled study with two 4-week intervention phases. In all, seventy-one subjects recruited from the screening stage were divided into two groups--the Yellow group and the Blue group. In the 1st phase, one group received probiotic drinks twice a day and the other group received placebo drinks. Blood and urine samples were collected at baseline, 2nd and 4th week of the intervention. After a 2-week wash-out period, the treatments were switched between the groups, and blood and urine samples were collected at the 6th, 8th and 10th week (2nd phase) of the intervention. No significant differences in aflatoxin biomarker concentrations were observed during the intervention. A within-group analysis was further carried out. Aflatoxin biomarker concentrations were not significantly different in the Yellow group. Nevertheless, ANOVA for repeated measurements indicated that AFB1-lys concentrations were significantly different (P=0·035) with the probiotic intervention in the Blue group. The 2nd week AFB1-lys concentrations (5·14 (SD 2·15) pg/mg albumin (ALB)) were significantly reduced (P=0·048) compared with the baseline (6·24 (SD 3·42) pg/mg ALB). Besides, the 4th week AFB1-lys concentrations were significantly lower (P<0·05) with probiotic supplementation than with the placebo. Based on these findings, a longer intervention study is warranted to investigate the effects of continuous LcS consumption to prevent dietary aflatoxin exposure.

  1. Randomised, double-blind, placebo-controlled studies on flurbiprofen 8.75 mg lozenges in patients with/without group A or C streptococcal throat infection, with an assessment of clinicians' prediction of 'strep throat'.

    Science.gov (United States)

    Shephard, A; Smith, G; Aspley, S; Schachtel, B P

    2015-01-01

    Diagnosing group A streptococcus (Strep A) throat infection by clinical examination is difficult, and misdiagnosis may lead to inappropriate antibiotic use. Most patients with sore throat seek symptom relief rather than antibiotics, therefore, therapies that relieve symptoms should be recommended to patients. We report two clinical trials on the efficacy and safety of flurbiprofen 8.75 mg lozenge in patients with and without streptococcal sore throat. The studies enrolled adults with moderate-to-severe throat symptoms (sore throat pain, difficulty swallowing and swollen throat) and a diagnosis of pharyngitis. The practitioner assessed the likelihood of Strep A infection based on historical and clinical findings. Patients were randomised to flurbiprofen 8.75 mg or placebo lozenges under double-blind conditions and reported the three throat symptoms at baseline and at regular intervals over 24 h. A total of 402 patients received study medication (n = 203 flurbiprofen, n = 199 placebo). Throat culture identified Strep A in 10.0% of patients and group C streptococcus (Strep C) in a further 14.0%. The practitioners' assessments correctly diagnosed Strep A in 11/40 cases (sensitivity 27.5%, and specificity 79.7%). A single flurbiprofen lozenge provided significantly greater relief than placebo for all three throat symptoms, lasting 3-4 h for patients with and without Strep A/C. Multiple doses of flurbiprofen lozenges over 24 h also led to symptom relief, although not statistically significant in the Strep A/C group. There were no serious adverse events. The results highlight the challenge of identifying Strep A based on clinical features. With the growing problem of antibiotic resistance, non-antibiotic treatments should be considered. As demonstrated here, flurbiprofen 8.75 mg lozenges are an effective therapeutic option, providing immediate and long-lasting symptom relief in patients with and without Strep A/C infection. © 2014 John Wiley & Sons Ltd.

  2. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Blauvelt, Andrew; de Bruin-Weller, Marjolein; Gooderham, Melinda; Cather, Jennifer C; Weisman, Jamie; Pariser, David; Simpson, Eric L; Papp, Kim A; Hong, H Chih-Ho; Rubel, Diana; Foley, Peter; Prens, Errol; Griffiths, Christopher E M; Etoh, Takafumi; Pinto, Pedro Herranz; Pujol, Ramon M; Szepietowski, Jacek C; Ettler, Karel; Kemény, Lajos; Zhu, Xiaoping; Akinlade, Bolanle; Hultsch, Thomas; Mastey, Vera; Gadkari, Abhijit; Eckert, Laurent; Amin, Nikhil; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D; Shumel, Brad

    2017-06-10

    Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986. Between Oct 3, 2014

  3. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.

    Science.gov (United States)

    Wilke, Hansjochen; Muro, Kei; Van Cutsem, Eric; Oh, Sang-Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Lipatov, Oleg; Kim, Tae-You; Cunningham, David; Rougier, Philippe; Komatsu, Yoshito; Ajani, Jaffer; Emig, Michael; Carlesi, Roberto; Ferry, David; Chandrawansa, Kumari; Schwartz, Jonathan D; Ohtsu, Atsushi

    2014-10-01

    VEGFR-2 has a role in gastric cancer pathogenesis and progression. We assessed whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel. This randomised, placebo-controlled, double-blind, phase 3 trial was done at 170 centres in 27 countries in North and South America, Europe, Asia, and Australia. Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy (platinum plus fluoropyrimidine with or without an anthracycline) were randomly assigned with a centralised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15, plus paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. A permuted block randomisation, stratified by geographic region, time to progression on first-line therapy, and disease measurability, was used. The primary endpoint was overall survival. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one treatment with study drug. This trial is registered with ClinicalTrials.gov, number NCT01170663, and has been completed; patients who are still receiving treatment are in the extension phase. Between Dec 23, 2010, and Sept 23, 2012, 665 patients were randomly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel. Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9·6 months [95% CI 8·5-10·8] vs 7·4 months [95% CI 6·3-8·4], hazard ratio 0·807 [95% CI 0·678-0·962]; p=0·017). Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo

  4. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child.

    Science.gov (United States)

    1998-08-01

    There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the

  5. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent; Delaloge, Suzette; Moy, Beverly; Iwata, Hiroji; von Minckwitz, Gunter; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Tomašević, Zorica; Denduluri, Neelima; Šeparović, Robert; Gokmen, Erhan; Bashford, Anna; Ruiz Borrego, Manuel; Kim, Sung-Bae; Jakobsen, Erik Hugger; Ciceniene, Audrone; Inoue, Kenichi; Overkamp, Friedrich; Heijns, Joan B; Armstrong, Anne C; Link, John S; Joy, Anil Abraham; Bryce, Richard; Wong, Alvin; Moran, Susan; Yao, Bin; Xu, Feng; Auerbach, Alan; Buyse, Marc; Chan, Arlene

    2017-12-01

    ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib

  6. Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Ludolph, Albert C; Schuster, Joachim; Dorst, Johannes; Dupuis, Luc; Dreyhaupt, Jens; Weishaupt, Jochen H; Kassubek, Jan; Weiland, Ulrike; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Schrank, Berthold; Boentert, Matthias; Emmer, Alexander; Hermann, Andreas; Zeller, Daniel; Prudlo, Johannes; Winkler, Andrea S; Grehl, Torsten; Heneka, Michael T; Wollebæk Johannesen, Siw; Göricke, Bettina

    2018-06-18

    Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the

  7. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial

    Science.gov (United States)

    Haas, Naomi B; Manola, Judith; Uzzo, Robert G; Flaherty, Keith T; Wood, Christopher G; Kane, Christopher; Jewett, Michael; Dutcher, Janice P; Atkins, Michael B; Pins, Michael; Wilding, George; Cella, David; Wagner, Lynne; Matin, Surena; Kuzel, Timothy M; Sexton, Wade J; Wong, Yu-Ning; Choueiri, Toni K; Pili, Roberto; Puzanov, Igor; Kohli, Manish; Stadler, Walter; Carducci, Michael; Coomes, Robert; DiPaola, Robert S

    2016-01-01

    Summary Background Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence. Methods In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada. Eligible patients had pathological stage high-grade T1b or greater with completely resected non-metastatic renal-cell carcinoma and adequate cardiac, renal, and hepatic function. Patients were stratified by recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach, and computerised double-blind randomisation was done centrally with permuted blocks. Patients were randomly assigned (1:1:1) to receive 54 weeks of sunitinib 50 mg per day orally throughout the first 4 weeks of each 6 week cycle, sorafenib 400 mg twice per day orally throughout each cycle, or placebo. Placebo could be sunitinib placebo given continuously for 4 weeks of every 6 week cycle or sorafenib placebo given twice per day throughout the study. The primary objective was to compare disease-free survival between each experimental group and placebo in the intention-to-treat population. All treated patients with at least one follow-up assessment were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00326898. Findings Between April 24, 2006, and Sept 1, 2010, 1943 patients from the National Clinical Trials Network were randomly assigned to sunitinib (n=647), sorafenib (n=649), or placebo (n=647). Following high rates of toxicity-related discontinuation after 1323 patients had enrolled (treatment discontinued by 193 [44%] of 438 patients on sunitinib, 199 [45%] of 441 patients on sorafenib), the starting dose of each

  8. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study

    NARCIS (Netherlands)

    Sakkers, Ralph; Kok, Dieke; Engelbert, Raoul; van Dongen, Alice; Jansen, Maarten; Pruijs, Hans; Verbout, Ab; Schweitzer, Dave; Uiterwaal, Cuno

    2004-01-01

    Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. 34 children recruited from the Dutch national centre for

  9. Homoeopathic Genus Epidemicus ′Bryonia alba′ as a prophylactic during an outbreak of Chikungunya in India: A cluster -randomised, double -blind, placebo- controlled trial

    Directory of Open Access Journals (Sweden)

    K R Janardanan Nair

    2014-01-01

    Conclusion: Bryonia alba 30C as genus epidemicus was better than placebo in decreasing the incidence of chikungunya in Kerala. The efficacy of genus epidemicus needs to be replicated in different epidemic settings.

  10. A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE).

    Science.gov (United States)

    Allen, S J; Wareham, K; Wang, D; Bradley, C; Sewell, B; Hutchings, H; Harris, W; Dhar, A; Brown, H; Foden, A; Gravenor, M B; Mack, D; Phillips, C J

    2013-12-01

    Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10

  11. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    Science.gov (United States)

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2017-01-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score during the 30 second periods after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  13. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial.

    Science.gov (United States)

    Tannock, Ian F; Fizazi, Karim; Ivanov, Sergey; Karlsson, Camilla Thellenberg; Fléchon, Aude; Skoneczna, Iwona; Orlandi, Francisco; Gravis, Gwenaelle; Matveev, Vsevolod; Bavbek, Sevil; Gil, Thierry; Viana, Luciano; Arén, Osvaldo; Karyakin, Oleg; Elliott, Tony; Birtle, Alison; Magherini, Emmanuelle; Hatteville, Laurence; Petrylak, Daniel; Tombal, Bertrand; Rosenthal, Mark

    2013-07-01

    Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285 FINDINGS: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We

  14. Outcome of transcutaneous electrical nerve stimulation in chronic pain: short-term results of a double-blind, randomised, placebo-controlled trial.

    NARCIS (Netherlands)

    Oosterhof, J.; Boo, T.M. de; Oostendorp, R.A.B.; Wilder-Smith, O.H.G.; Crul, B.J.P.

    2006-01-01

    The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham

  15. Radial extracorporeal shock-wave therapy in patients with chronic rotator cuff tendinitis: a prospective randomised double-blind placebo-controlled multicentre trial

    NARCIS (Netherlands)

    Kolk, A. van der; Yang, K.G.; Tamminga, R.; Hoeven, H. van der

    2013-01-01

    The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were

  16. A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in Active Crohn's Disease

    DEFF Research Database (Denmark)

    Schölmerich, Jürgen; Fellermann, Klaus; Seibold, Frank W

    2017-01-01

    Background and Aims: To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD]. Methods: Adults with active CD [n.......2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo...... for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns. Conclusions: Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose...

  17. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome--a randomised, double-blind, placebo controlled trial

    DEFF Research Database (Denmark)

    Begtrup, Luise Mølenberg; de Muckadell, Ove B Schaffalitzky; Kjeldsen, Jens

    2013-01-01

    OBJECTIVE. Meta-analyses have indicated effect of probiotics on irritable bowel syndrome (IBS). However, few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting. We aimed to investigate the effect of probiotics compared...... with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up. MATERIAL AND METHODS. We randomized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp....../67) in the probiotic group versus 41% (26/64) in the placebo group, p = 0.18. Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment. Patients improved in HrQOL, but with no statistically significant difference between the groups. CONCLUSION. During a 6-month treatment...

  18. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Groome, Michelle J; Koen, Anthonet; Fix, Alan; Page, Nicola; Jose, Lisa; Madhi, Shabir A; McNeal, Monica; Dally, Len; Cho, Iksung; Power, Maureen; Flores, Jorge; Cryz, Stanley

    2017-08-01

    Efficacy of live oral rotavirus vaccines is reduced in low-income compared with high-income settings. Parenteral non-replicating rotavirus vaccines might offer benefits over oral vaccines. We assessed the safety and immunogenicity of the P2-VP8-P[8] subunit rotavirus vaccine at different doses in South African toddlers and infants. This double-blind, randomised, placebo-controlled, dose-escalation trial was done at a single research unit based at a hospital in South Africa in healthy HIV-uninfected toddlers (aged 2 to rotavirus vaccination). Block randomisation (computer-generated, electronic allocation) was used to assign eligible toddlers (in a 6:1 ratio) and infants (in a 3:1 ratio) in each dose cohort (10 μg, followed by 30 μg, then 60 μg if doses tolerated) to parenteral P2-VP8-P[8] subunit rotavirus or placebo injection. The two highest tolerated doses were then assessed in an expanded cohort (in a 1:1:1 ratio). Parents of participants and clinical, data, and laboratory staff were masked to treatment assignment. P2-VP8-P[8] vaccine versus placebo was assessed first in toddlers (single injection) and then in infants (three injections 4 weeks apart). The primary safety endpoints were local and systemic reactions within 7 days after each injection, adverse events within 28 days after each injection, and all serious adverse events, assessed in toddlers and infants who received at least one dose. In infants receiving all study injections, primary immunogenicity endpoints were anti-P2-VP8-P[8] IgA and IgG and neutralising antibody seroresponses and geometric mean titres 4 weeks after the third injection. This trial is registered at ClinicalTrials.gov, number NCT02109484. Between March 17, 2014, and Sept 29, 2014, 42 toddlers (36 to vaccine and six to placebo) and 48 infants (36 to vaccine and 12 to placebo) were enrolled in the dose-escalation phase, in which the 30 μg and 60 μg doses where found to be the highest tolerated doses. A further 114 infants were

  19. Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

    Directory of Open Access Journals (Sweden)

    van der Woude Hanneke J

    2010-05-01

    Full Text Available Abstract Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1 after inhaling adenosine 5'-monophosphate (AMP, were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours. Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg, formoterol (4.5 μg, salbutamol (2 × 100 μg or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours

  20. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

    Science.gov (United States)

    Santolaya, María Elena; O'Ryan, Miguel L; Valenzuela, María Teresa; Prado, Valeria; Vergara, Rodrigo; Muñoz, Alma; Toneatto, Daniela; Graña, Gabriela; Wang, Huajun; Clemens, Ralf; Dull, Peter M

    2012-02-18

    Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (pvaccine-related serious adverse events were reported and no significant safety signals were identified. On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against

  1. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Astrup, Arne; Madsbad, Sten; Breum, Leif

    2008-01-01

    BACKGROUND: Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline...

  2. Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

    Directory of Open Access Journals (Sweden)

    Nadeson Raymond

    2005-04-01

    Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter

  3. Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

    Science.gov (United States)

    Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

    2011-09-21

    Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to

  4. Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS [Eudract number: 2008-006891-31

    Directory of Open Access Journals (Sweden)

    Kelly Joanna

    2011-09-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival at the end of the study (15 months from entry, compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3 at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L, plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network. 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D, and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive, vital

  5. Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449

    Directory of Open Access Journals (Sweden)

    Attree EA

    2006-06-01

    Full Text Available Abstract Background Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. Methods Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline. They were then assigned to either placebo (56 days followed by experimental (56 days or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health were obtained and analysed by repeated measures ANOVAs. Results Symptom severity for all symptoms (except constipation were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 – 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p Conclusion Dietary nucleotide supplementation improves some of the

  6. Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates--a randomised double blind placebo controlled trial.

    Science.gov (United States)

    Patole, Sanjay; Keil, Anthony D; Chang, Annie; Nathan, Elizabeth; Doherty, Dorota; Simmer, Karen; Esvaran, Meera; Conway, Patricia

    2014-01-01

    Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC) and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. To assess product quality, and confirm that Bifidobacterium breve (B. breve) M-16V supplementation will increase fecal B. breve counts without adverse effects. Strain identity (16S rRNA gene sequencing), viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation breve M-16V (3×109 cfu/day) or placebo (dextrin) supplementation until the corrected age 37 weeks. Stool samples were collected before (S1) and after 3 weeks of supplementation (S2) for studying fecal B. breve levels using quantitative PCR (Primary outcome). Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. A total of 159 neonates (Probiotic: 79, Placebo: 80) were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%), S2: 25/66 (38%), pbreve counts in both groups were below detection (breve M-16V is a suitable probiotic strain for routine use in preterm neonates. Australia New Zealand Clinical Trial Registry ACTRN 12609000374268.

  7. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    2017-05-27

    Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10

  8. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study: a double-blind, randomised, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Shahin Lockman, MD

    2017-05-01

    Full Text Available Summary: Background: Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear. Methods: HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter or placebo from age 14–34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines or 12 months (WHO guidelines. The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761. Findings: From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423 or placebo (n=1425. The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5% children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group, and 2053 (72% received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference −0·2%, 95% CI −1·5 to 1·0, p=0·70. We saw no difference in hospital admissions between groups (12·5% in the co-trimoxazole group vs 17·4% in the placebo group, p=0·19 or grade 3–4 clinical adverse events (16·5% vs 18·4%, p=0·18. Grade 3–4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93, but grade 3–4

  9. Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture.

    Science.gov (United States)

    Alsousou, Joseph; Keene, David J; Hulley, Philippa A; Harrison, Paul; Wagland, Susan; Byrne, Christopher; Schlüssel, Michael Maia; Dutton, Susan J; Lamb, Sarah E; Willett, Keith

    2017-11-16

    Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies. This is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle-tendon function, quality of life, pain and overall patient's functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations. The protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals. ISRCTN: 54992179, assigned

  10. Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates--a randomised double blind placebo controlled trial.

    Directory of Open Access Journals (Sweden)

    Sanjay Patole

    Full Text Available BACKGROUND: Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. AIM: To assess product quality, and confirm that Bifidobacterium breve (B. breve M-16V supplementation will increase fecal B. breve counts without adverse effects. METHODS AND PARTICIPANTS: Strain identity (16S rRNA gene sequencing, viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day or placebo (dextrin supplementation until the corrected age 37 weeks. Stool samples were collected before (S1 and after 3 weeks of supplementation (S2 for studying fecal B. breve levels using quantitative PCR (Primary outcome. Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. RESULTS: A total of 159 neonates (Probiotic: 79, Placebo: 80 were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%, S2: 25/66 (38%, p<0.001] Probiotic: [S1: 29/74 (40%, S2: 67/74 (91%, p<0.001]. Median S1 B. breve counts in both groups were below detection (<4.7 log cells x g(-1, increasing significantly in S2 for the probiotic group (log 8.6 while remaining <4.7 log in the control group (p<0.001. There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group. CONCLUSION: B. breve M-16V is a suitable probiotic

  11. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

    OpenAIRE

    Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podg?rski, Tomasz

    2017-01-01

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, whil...

  12. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial.

    Science.gov (United States)

    Hohlfeld, Jens M; Vogel-Claussen, Jens; Biller, Heike; Berliner, Dominik; Berschneider, Korbinian; Tillmann, Hanns-Christian; Hiltl, Simone; Bauersachs, Johann; Welte, Tobias

    2018-02-21

    Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 <80% predicted and post-bronchodilator FEV 1 : forced vital capacity <0·7). Patients with stable cardiovascular disease were eligible, but those with arrhythmias, heart failure, unstable ischaemic heart disease, or uncontrolled hypertension were not. We randomly assigned participants (1:1) to either receive a combined inhaled dual bronchodilator containing the LABA indacaterol (110 μg as maleate salt) plus the LAMA glycopyrronium (50 μg as bromide salt) once per day for 14 days, followed by a 14-day washout, then a matched placebo for 14 days, or to receive the same treatments in reverse order. The randomisation was done using lists and was concealed from patients and investigators. The primary endpoint was the effect of indacaterol-glycopyrronium versus placebo on left-ventricular end-diastolic volume measured by MRI done on day 1 (visit 4) and day 15 (visit 5) in treatment period 1 and on day 29 (visit 6) and day 43 (visit 7) in treatment period 2 in the per-protocol population. Left-ventricular end-diastolic volume was indexed to body surface area. Safety was assessed in all participants who received

  13. A protocol for a randomised double-blind placebo-controlled feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing and remitting multiple sclerosis (RRMS).

    Science.gov (United States)

    Coe, S; Collett, J; Izadi, H; Wade, D T; Clegg, M; Harrison, J M; Buckingham, E; Cavey, A; DeLuca, G C; Palace, J; Dawes, H

    2018-01-01

    Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis. Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial.We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. Registered with ISRCTN Registry. Trial

  14. Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial.

    Science.gov (United States)

    Buyse, Gunnar M; Voit, Thomas; Schara, Ulrike; Straathof, Chiara S M; D'Angelo, M Grazia; Bernert, Günther; Cuisset, Jean-Marie; Finkel, Richard S; Goemans, Nathalie; McDonald, Craig M; Rummey, Christian; Meier, Thomas

    2015-05-02

    Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids. In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), which was prospectively defined to exclude patients with at least 20% difference in the yearly change in PEF%p, measured with hospital-based and weekly home-based spirometry. This study is registered with ClinicalTrials.gov, number NCT01027884. 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population, and 30 and 27 comprised the mITT population. Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT (-3·05%p [95% CI -7·08 to 0·97], p=0·134, vs placebo -9·01%p [-13·18 to -4·84], p=0·0001; difference 5·96%p [0·16 to 11·76], p=0·044) and ITT populations (-2·57%p [-6·68 to 1·54], p=0·215, vs -8·84%p [-12·73 to -4·95], pmuscular dystrophy. Santhera Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Effects of angiotensin II blockade on intermediate cardiovascular endpoints in haemodialysis patients: a randomised double-blind placebo-controlled one-year intervention trial (SAFIR study)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

    Agents blocking the renin-angiotensin-aldosterone system are frequently used in end-stage renal disease patients, but whether they exert beneficial cardiovascular (CV) effects is unclear. The long-term effects of the angiotensin II receptor blocker irbesartan was investigated in 82 haemodialysis...... renal function. Brachial BP decreased significantly in both groups, but there was no significant difference between placebo and irbesartan treated. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different in the two groups. Intermediate CV endpoints...... such as central aortic BP, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal prohormone of brain natriuretic peptide, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic BP during the study period correlated...

  16. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Fox, Kim; Ford, Ian; Steg, P Gabriel

    2008-01-01

    .9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect...... the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect...... disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater....

  17. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2015-01-01

    was stratified by disease stage and geographical region. The primary endpoint was recurrence-free survival, assessed by an independent review committee, and analysed by intention to treat. Enrollment is complete but the study is ongoing for follow-up for analysis of secondary endpoints. This trial is registered...... with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168. FINDINGS: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to ipilimumab (n=475) or placebo (n=476), all of whom were included in the intention-to-treat analyses. At a median follow-up of 2·74 years...... at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value. FUNDING: Bristol-Myers Squibb....

  18. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomised, double-blind, placebo controlled trial

    Science.gov (United States)

    Cunliffe, Nigel A; Witte, Desiree; Ngwira, Bagrey M; Todd, Stacy; Bostock, Nancy J; Turner, Ann M; Chimpeni, Philips; Victor, John C; Steele, A Duncan; Bouckenooghe, Alain; Neuzil, Kathleen M

    2014-01-01

    Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 - 8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 – 14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 – 57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 – 56.0) was lower than in the first year of life (49.4%; 19.2 – 68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged

  19. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Heppner, D Gray; Kemp, Tracy L; Martin, Brian K; Ramsey, William J; Nichols, Richard; Dasen, Emily J; Link, Charles J; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A; Nowak, Teresa A; Monath, Thomas P

    2017-08-01

    The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log 10 dose range in two sequential cohorts. In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 10 3 , 3 × 10 4 , 3 × 10 5 , or 3 × 10 6 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 10 6 , 9 × 10 6 , 2 × 10 7 , or 1 × 10 8 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 10 3 [n=64], 3 × 10 4 [n=64], 3 × 10 5 [n=64], or 3 × 10 6 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 10 6 [n=20], 9 × 10 6 [n=47], 2 × 10 7 [n=47], or 1 × 10 8 PFU [n=48]) and 20 received placebo. Most

  20. Repetitive transcranial magnetic stimulation for depression after basal ganglia ischaemic stroke: protocol for a multicentre randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Tang, Ying; Chen, Aimin; Zhu, Shuzhen; Yang, Li; Zhou, Jiyuan; Pan, Suyue; Shao, Min; Zhao, Lianxu

    2018-02-03

    Studies suggest that repetitive transcranial magnetic stimulation (rTMS) is effective for the treatment of depression and promotes the repair of white matter. This study aims to assess the effectiveness of rTMS in treating depression after basal ganglia ischaemic stroke and to examine whether such effects are related to restoration of white matter integrity. Sixty-six participants will be recruited from Zhujiang Hospital, Nanfang Hospital and Sichuan Bayi Rehabilitation Hospital and randomised in a 1:1 ratio to receive active rTMS treatment or sham rTMS treatment in addition to routine supportive treatments. The data will be collected at 0, 2 and 4 weeks after the commencement of treatment. The primary outcome is the measurement of 24-item Hamilton Depression Rating Scale scores, and the secondary outcomes include diffusion tensor imaging results and the results of neuropsychological tests including the National Institutes of Health Stroke Scale, Activities of Daily Living Scale, Montreal Cognitive Assessment, Clinical Global Impressions scales, Aphasia Battery in Chinese, Social Support Revalued Scale and Medical Coping Modes Questionnaire. This study has been approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University. The findings will be disseminated by publication in a peer-reviewed journal and by presentation at international conferences. NCT03159351. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Moderate dose melatonin for the abatement and treatment of delirium in elderly general medical inpatients: study protocol of a placebo controlled, randomised, double blind trial.

    Science.gov (United States)

    Clayton-Chubb, Daniel I; Lange, Peter W

    2016-02-29

    Delirium is a frequent, costly and morbid problem. No agent has been shown to modify the natural history of the condition, and current treatments have significant side effects. Prophylactic melatonin in low doses has been shown to prevent delirium developing. This trial then aims to determine the feasibility of a trial to assess if melatonin at a moderate dose effectively treats the symptoms of delirium and modifies the natural history, including abating symptoms after treatment cessation. Elderly (≥70 years of age) patients admitted to the Royal Melbourne Hospital with delirium, and not requiring surgery, will be identified from the current practice of the investigators and through referral by other general medical unit staff. To facilitate this, other staff will be briefed on the project by investigators. Patients will be recruited with suitable informed and documented consent (person responsible) by the study investigators. They will receive orally either 5 mg melatonin (18 patients) or placebo (18 patients) nightly for 5 nights (or until discharged). During treatment, participants will be assessed by study staff using a validated scale of delirium severity (the Memorial Delirium Assessment Scale), and a validated measure of delirium state (Confusion Assessment Method) to determine if melatonin decreases the severity or the duration of delirium. Assessment will continue for a further two days after treatment has ceased, to determine if the treatment causes persisting abatement of symptoms, and to assess for adverse events. The on-going study described herein will contribute to our knowledge of available treatment options for elderly inpatients with delirium, where current pharmacological interventions show weak or no effect on hastening the resolution of delirium. As melatonin is safe, cheap, and potentially effective, it would be easily implementable in routine practice and could lead to significant outcome benefits for delirious inpatients. The trial is

  2. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

    Science.gov (United States)

    Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

    2017-07-14

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p athletes.

  3. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Coens, Corneel; Suciu, Stefan; Chiarion-Sileni, Vanna

    2017-01-01

    consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial. Here, we report the results...... were randomly assigned (1:1) centrally by an interactive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region...

  4. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes

    NARCIS (Netherlands)

    Kerkhoffs, G. M. M. J.; Struijs, P. A. A.; de Wit, C.; Rahlfs, V. W.; Zwipp, H.; van Dijk, C. N.

    2004-01-01

    Objective: To compare the effectiveness and safety of the triple combination Phlogenzym ( rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo. Design: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured

  5. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-01-01

    Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. Trial registration number NCT01023256 PMID:24534756

  6. PISA. The effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690

    Directory of Open Access Journals (Sweden)

    Kappelle Jaap

    2002-03-01

    Full Text Available Abstract Background During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily and low dose (3 g daily paracetamol (acetaminophen in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. Aim The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. Design Seventy-five (3 × 25 patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

  7. Meningococcal serogroup B-specific responses after vaccination with bivalent rLP2086: 4 year follow-up of a randomised, single-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Marshall, Helen S; Richmond, Peter C; Beeslaar, Johannes; Jiang, Qin; Jansen, Kathrin U; Garcés-Sánchez, Maria; Martinón-Torres, Federico; Szenborn, Leszek; Wysocki, Jacek; Eiden, Joseph; Harris, Shannon L; Jones, Thomas R; Lee, Su-San; Perez, John L

    2017-01-01

    Bivalent rLP2086 is a recombinant factor H binding protein-based vaccine approved in the USA for prevention of meningococcal serogroup B disease in 10-25-year-olds. We aimed to assess the persistence of bactericidal antibodies up to 4 years after a three-dose schedule of bivalent rLP2086. We did this randomised, single-blind, placebo-controlled, phase 2 trial at 25 sites in Australia, Poland, and Spain. In stage 1 of the study (February, 2009-May, 2010), healthy adolescents (aged 11-18 years) were randomly assigned, via an interactive voice and web-response system with computer-generated sequential random numbers, to receive either ascending doses of vaccine (60 μg, 120 μg, and 200 μg) or placebo at months 0, 2, and 6. Dispensing staff were not masked to group allocation, but allocation was concealed from principal investigators, participants and their guardians, and laboratory personnel. In stage 2 of the study (reported here), we enrolled healthy adolescents who had received three doses of 120 μg bivalent rLP2086 (the optimum dose level identified in stage 1) or saline. Immunogenicity was determined in serum bactericidal antibody assay using human complement (hSBA) by use of four meningococcal serogroup B test strains expressing vaccine-heterologous factor H binding protein variants: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44). Immunogenicity in stage 2 was assessed at months 6, 12, 24, and 48 post-vaccination. We did analysis by intention to treat. This trial is registered as ClinicalTrials.gov number NCT00808028. Between March 17, 2010, and Feb 8, 2011, 170 participants who received 120 μg of bivalent rLP2086 and 80 participants who received placebo in stage 1 of the study were entered into stage 2; 210 participants completed stage 2 up to 48 months. 1 month after the third vaccination, 93% (n=139/149) to 100% (n=48/48) of vaccine recipients achieved protective hSBA titres equal to or greater than the lower limit of quantification to each

  8. Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

    Science.gov (United States)

    Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

    2002-04-01

    To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

  9. Radiotherapy for Graves' orbitopathy : randomised placebo-controlled study

    NARCIS (Netherlands)

    Mourits, MP; van Kempen-Harteveld, ML; Garcia, MBG; Koppeschaar, HPF; Tick, L; Terwee, CB

    2000-01-01

    Background The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation. Methods In a double-blind randomised clinical trial, 30 patients with

  10. A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

    Science.gov (United States)

    Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

    2017-07-17

    Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention

    Science.gov (United States)

    von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

    2008-01-01

    Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482 PMID:18667086

  12. Heartburn treatment in primary care: randomised, double blind study for 8 weeks

    Science.gov (United States)

    Hatlebakk, Jan G; Hyggen, Arild; Madsen, Per H; Walle, Per O; Schulz, Tom; Mowinckel, Petter; Bernklev, Tomm; Berstad, Arnold

    1999-01-01

    Objective To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. Design Randomised, double blind, placebo controlled study. Setting 65 primary care practices in Norway. Participants 483 untreated patients with complaints of heartburn ⩾3 days a week, with at most grade 1 reflux oesophagitis. Interventions Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. Main outcome measures Adequate control of heartburn, defined as ⩽1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. Results In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, Pheartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo. Key messagesIn primary care patients, heartburn is commonly treated empiricallyMost randomised clinical trials of treatment for heartburn have been conducted in specialist care, and documentation for empirical treatment is limitedOmeprazole was significantly more effective than cisapride or placebo in controlling heartburn and other symptoms of gastro-oesophageal reflux after 2, 4, and 8 weeks, whereas cisapride did not differ significantly from placeboOmeprazole should be considered as a first choice for empirical treatment of heartburn in primary care PMID:10463897

  13. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

    Science.gov (United States)

    Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

    2014-03-01

    Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

  14. Double-blind, placebo-controlled food challenge with apple

    DEFF Research Database (Denmark)

    Skamstrup Hansen, K; Vestergaard, H; Stahl Skov, P

    2001-01-01

    The aim of the study was to develop and evaluate different methods of double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze-dried apple powder. All challenges were performed outside...... frequency of reactions to placebo, probably due to the ingredients used for blinding. The sensitivity of the models with freshly grated apple and freeze-dried apple powder was 0.74/0.60. An increase in sensitivity is desirable. The freeze-dried apple powder proved to be useful for SPT, HR, and oral...

  15. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

    Science.gov (United States)

    Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

    2016-02-01

    Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

  16. Effect of Blinding With a New Pragmatic Placebo Needle

    Science.gov (United States)

    Liu, Baoyan; Xu, Huanfang; Ma, Rui; Mo, Qian; Yan, Shiyan; Liu, Zhishun

    2014-01-01

    Abstract Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration. We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed. Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers’ perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01–2.64). The influences of age, sex, educational level, acupuncture

  17. Sildenafil citrate in combination with tamsulosin versus tamsulosin monotherapy for management of male lower urinary tract symptoms due to benign prostatic hyperplasia: A randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Fawzi, Amr; Kamel, Mostafa; Salem, Emad; Desoky, Esam; Omran, Mohamed; Elgalaly, Hazem; Sakr, Ahmed; Maarouf, Aref; Khalil, Salem

    2017-03-01

    To assess the additive effect of sildenafil citrate to tamsulosin in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) in men with or without erectile dysfunction (ED). In all, 150 men with untreated LUTS/BPH with or without ED were randomised to receive sildenafil 25 mg once daily (OD) or placebo OD (night time) combined with tamsulosin 0.4 mg OD (day time) for 6 months. Changes from pre-treatment scores in International Prostate Symptom Score (IPSS), IPSS-quality of life (QoL) score, maximum urinary flow rate ( Q max ), and the five-item version of the International Index of Erectile Function questionnaire (IIEF-5) were assessed at 3 and 6 months. Safety profiles were assessed by physical examination and monitoring clinical adverse events. Group A comprised of men who received tamsulosin and sildenafil (75 men), whilst those in Group B received tamsulosin and placebo (75). The IPSS was significantly improved in Group A compared to Group B, at -29.3% vs -13.7% ( P  = 0.039) at 3 months and -37% vs -19.6% ( P  = 0.043) at 6 months after treatment. Q max significantly improved in both groups compared with before treatment ( P  tamsulosin improved LUTS, erectile function, and patient QoL more than tamsulosin monotherapy with the merit of a comparable safety profile in patients with LUTS/BPH.

  18. Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention.

    Science.gov (United States)

    Syrjänen, Kari; Salminen, Johanna; Aresvuo, Ulla; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Salaspuro, Mikko; Suovaniemi, Osmo

    2016-05-01

    Harmans are condensation products of acetaldehyde and biogenic amines in saliva. Like other monoamine oxidase inhibitors, harmans help maintain behavioral sensitization to nicotine and mediate the addictive potential of cigarette smoke-derived acetaldehyde. The aim of this study was to test the hypothesis that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium™ lozenge; Biohit Oyj, Helsinki, Finland) blocks the formation of harmans and eliminates acetaldehyde-enhanced nicotine addiction in smokers. A double-blind, randomized, placebo-controlled trial comparing Acetium lozenges and placebo in smoking intervention was undertaken. A cohort of 423 cigarette smokers were randomly allocated to intervention (n=212) and placebo arms (n=211). Smoking-related data were recorded by questionnaires, together with nicotine dependence testing by Fagerström scale. The participants used a smoking diary to record the daily number of cigarettes, test lozenges and sensations of smoking. The data were analyzed separately for point prevalence of abstinence and prolonged abstinence endpoints. Altogether, 110 study participants completed the trial per protocol, 234 had minor violations, and the rest (n=79) were lost to follow-up. During the 6-month trial, 65 participants quit smoking; 38 (17.9%) in the intervention arm and 27 (12.8%) in the placebo arm [odds ratio (OR)=1.48; 95% confidence intervals (CI)=0.87-2.54; p=0.143]. Success in the per protocol group was better (42.9% vs. 31.1%, respectively; OR=1.65, 95% CI=0.75-3.62; p=0.205) than in the modified intention-to-treat group: 13.5% vs. 7.4% (p=0.128). If the efficacy of Acetium lozenge can be confirmed in an adequately powered study, this new approach would represent a major breakthrough in smoking quit intervention because slow-release L-cysteine is non-toxic with no side-effects or limitations of use. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All

  19. Double blind placebo controlled exposure to molds

    DEFF Research Database (Denmark)

    Meyer, H W; Jensen, K A; Nielsen, K F

    2005-01-01

    non-significant, and at the same level as after placebo exposure. The developed exposure system based on the Particle-Field and Laboratory Emission Cell (P-FLEC) makes it possible to deliver a precise and highly controlled dose of mold spores from water-damaged building materials, imitating realistic......The objective was to develop an experimental setup for human exposure to mold spores, and to study the clinical effect of this exposure in sensitive subjects who had previously experienced potentially building-related symptoms (BRS) at work. From three water-damaged schools eight employees....... In conclusion this is, to our knowledge, the first study to successfully conduct a human exposure to a highly controlled dose of fungal material aerosolized directly from wet building materials. This short-term exposure to high concentrations of two different molds induced no more reactions than exposure...

  20. Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

    Science.gov (United States)

    Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

    2018-04-30

    Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is

  1. Placebo response and remission rates in randomised trials of induction andmaintenance therapy for ulcerative colitis

    NARCIS (Netherlands)

    Jairath, Vipul; Zou, G. Y.; Parker, Claire E.; Macdonald, John K.; AlAmeel, Turki; Al Beshir, Mohammad; Almadi, Majid A.; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel R.; Koutsoumpas, Andreas; Minas, Elizabeth; Mosli, Mahmoud H.; Samaan, Mark; Khanna, Reena; Travis, Simon; D'Haens, Geert; Sandborn, William J.; Feagan, Brian G.

    2017-01-01

    Background It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors

  2. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Ludvik, Bernhard; Frías, Juan P; Tinahones, Francisco J; Wainstein, Julio; Jiang, Honghua; Robertson, Kenneth E; García-Pérez, Luis-Emilio; Woodward, D Bradley; Milicevic, Zvonko

    2018-05-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg, dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to dulaglutide 1·5 mg (n=142), dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger

  3. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

    Science.gov (United States)

    Schellenberg, R

    2001-01-20

    To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (Pagnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

  4. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.

    Science.gov (United States)

    Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

    2017-06-01

    Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (ptofacitinib. NCT01393626 and NCT01393899. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial.

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-06-01

    To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. NCT01023256. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study

    Science.gov (United States)

    Kavanaugh, A; Gladman, D; van der Heijde, D; Purcaru, O; Mease, P

    2015-01-01

    Objectives To evaluate the effect of certolizumab pegol (CZP) on productivity outside and within the home, and on participation in family, social and leisure activities in adult patients with psoriatic arthritis (PsA). Methods RAPID-PsA (NCT01087788) is a phase 3, double-blind, placebo-controlled trial. 409 patients with active PsA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). The arthritis-specific Work Productivity Survey (WPS) assessed the impact of PsA on paid work and household productivity, and participation in social activities during the preceding month. WPS responses were compared between treatment arms using a non-parametric bootstrap-t method. Results At baseline, 56.6%, 60.1% and 61.5% of placebo, CZP 200 mg Q2W and CZP 400 mg Q4W patients were employed. By week 24, employed CZP patients reported an average of 1.0–1.8 and 3.0–3.9 fewer days of absenteeism and presenteeism, respectively, per month compared with 1.0 and 0.3 fewer days for placebo patients (pproductivity or days lost for participation in family, social and leisure activities. Improvements with CZP were seen as early as week 4 and continued to week 24. Conclusions CZP treatment significantly improved productivity at paid work and within the home, and resulted in greater participation in social activities for PsA patients. Trial registration number NCT01087788. PMID:24942382

  7. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

    Science.gov (United States)

    Linhares, Alexandre C; Velázquez, F Raúl; Pérez-Schael, Irene; Sáez-Llorens, Xavier; Abate, Hector; Espinoza, Felix; López, Pío; Macías-Parra, Mercedes; Ortega-Barría, Eduardo; Rivera-Medina, Doris Maribel; Rivera, Luis; Pavía-Ruz, Noris; Nuñez, Ernesto; Damaso, Silvia; Ruiz-Palacios, Guillermo M; De Vos, Béatrice; O'Ryan, Miguel; Gillard, Paul; Bouckenooghe, Alain

    2008-04-05

    Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). 897 infants were excluded from the according-to-protocol analysis. Fewer cases (protavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

  8. double-blind placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    I Loturco

    2016-08-01

    Full Text Available The aim was to investigate the effects of far infrared (FIR ray emitting clothes on indirect markers of exercise-induced muscle damage and physical performance recovery after a plyometric bout applied to soccer players. Twenty-one male players (18.9±0.6 years; 70.8±5.01 kg; 178.3±0.06 cm performed 100 drop-jumps. Six hours after the bout, athletes put on FIR clothes (FIR (density of 225 g • m-2, 88% far infrared rays emitting polyamide 66 Emana yarn (PA66 fibre, 12% Spandex, emissivity of 0.88 and power emitted of 341 W/m2μm at 37°C in the 5-20 μm wavelength range, patent WO 2009/077834 A2 (N=10 or placebo clothes (PLA (N=11. Mid-thigh circumferences, creatine kinase (CK, and delayed-onset muscle soreness (DOMS were assessed before, immediately after and 24, 48, and 72 h after the bout. Squat (SJ and countermovement jump (CMJ heights were measured before and at 24, 48, and 72 h after, while 1RM leg press (maximum strength was measured before and at 72 h after the plyometrics. No differences between groups were found in mid-thigh circumferences, SJ, CMJ or 1RM. CK increased significantly 24 h after the plyometrics in comparison to before (p<0.05 in both groups. PLA showed significant DOMS increases at 24, 48, and 72 h, while FIR showed significant increases at 24 and 48 h (p<0.05. DOMS effect sizes were greater in FIR (moderate at 48 h, ES=0.737 and large at 72 h, ES=0.844, suggesting that FIR clothes may reduce perceived DOMS after an intense plyometric session performed by soccer players.

  9. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

    Science.gov (United States)

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

  10. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol

    Science.gov (United States)

    Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V; Baandrup, Lone; Fagerlund, Birgitte; Jørgensen, Niklas R; Andersen, Ulrik B; Rostrup, Egill; Glenthøj, Birte Y; Ebdrup, Bjørn H

    2014-01-01

    Introduction Antipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight-lowering effects have also been recognised in patients with non-diabetes. The primary endpoint of this trial is weight loss after 3 months of treatment with a GLP-1 receptor agonist (exenatide once weekly) in patients with non-diabetic schizophrenia with antipsychotic-associated obesity. Secondary endpoints include physiological and metabolic measurements, various psychopathological and cognitive measures, and structural and functional brain MRI. Methods and analysis 40 obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised to subcutaneous injection of exenatide once weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. Ethics and dissemination The trial has been approved by the Danish Health and Medicines Authority, the National Committee on Health Research Ethics and the Danish Data Protection Agency. Trial participation presupposes theoral and written patient informed consent. An external, independent monitoring committee (Good Clinical Practice Unit at Copenhagen University Hospital) will monitor the study according to the GCP Guidelines. Trial data, including positive, negative and inconclusive results, will be presented at national and international scientific meetings and conferences. Papers will be submitted to peer-reviewed journals. Trial registration ClinicalTrials.gov identifier: NCT01794429; National Committee on Health Research Ethics project number: 36378; EudraCT nr: 2012-005404-17; The

  11. Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

    Science.gov (United States)

    Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

    2011-01-01

    Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

  12. NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

    NARCIS (Netherlands)

    Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

    2014-01-01

    INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

  13. RETRACTED: Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose-ranging study

    Directory of Open Access Journals (Sweden)

    MD Yoshitaka Fujii

    2004-07-01

    Fujii Y, Tanaka H, Somekawa Y. Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomised, double-blind, placebo-controlled, dose-ranging study. Current Therapeutic Research 2004;65:321–9. https://www.sciencedirect.com/science/article/pii/S0011393X04800018

  14. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

    2010-01-01

    AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure =140 mm......Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

  15. randomised double blind study to compare effectiveness of honey

    African Journals Online (AJOL)

    2014-02-02

    Feb 2, 2014 ... EAsT AFRICAN MEDICAL JOURNAL. February 2014 .... based randomised double- blinded clinical trial evaluating effectiveness of ... study drugs was undertaken following a random ... included sodium citrate, citric acid monohydrate, ... post-hoc test to carry out pair-wise comparisons of .... self-care market.

  16. Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

    Science.gov (United States)

    D'Angelo, Simona; Fracassi, Federico; Bresciani, Francesca; Galuppi, Roberta; Diana, Alessia; Linta, Nikolina; Bettini, Giuliano; Morini, Maria; Pietra, Marco

    2018-03-03

    Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

    with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

  18. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

    DEFF Research Database (Denmark)

    Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

    2010-01-01

    status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets....... Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained...

  19. Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention.

    Science.gov (United States)

    Islam, Md Zahirul; Shamim, Abu Ahmed; Viljakainen, Heli T; Akhtaruzzaman, Mohammad; Jehan, Atia H; Khan, Habib Ullah; Al-Arif, Ferdaus Ahmad; Lamberg-Allardt, Christel

    2010-07-01

    Due to little outdoor activity and low dietary intake of vitamin D (VD), Bangladeshi low-income women are at risk for osteoporosis at an early age. The present study assessed the effect of VD, Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers. This placebo-controlled 1-year intervention randomly assigned 200 apparently healthy subjects (aged 16-36 years) to four groups: VD group, daily 10 microg VD; VD and Ca (VD-Ca) group, daily 10 microg VD+600 mg Ca; multiple micronutrient and Ca (MMN-Ca) group, 10 microg VD and other micronutrients+600 mg Ca; a placebo group. Serum 25-hydroxyvitamin D (S-25OHD), intact parathyroid hormone (S-iPTH), Ca, phosphate and alkaline phosphatase were measured. Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry. All measurements were made at baseline and at 12 months. Significantly (P S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention. Supplementation had an effect (P S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group. Bone mineral augmentation increased at the femur in the supplemented groups. Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects. MMN-Ca may have analogous positive health implications with additional non-skeletal benefits.

  20. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

    Science.gov (United States)

    Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

    2007-11-01

    To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. Six UK paediatric departments. 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; pPEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (pPEG+E (41%) and placebo during treatment (45%). PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

  1. Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

    Science.gov (United States)

    Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

    To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

  2. Reduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524?) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomised, double-blind, placebo-controlled trial

    OpenAIRE

    Kean, James D.; Sarris, Jerome; Scholey, Andrew; Silberstein, Richard; Downey, Luke A.; Stough, Con

    2016-01-01

    Introduction This study investigated the effects of a marine oil extract (PCSO-524?) on inattention, hyperactivity, mood and cognition in children and adolescents. PCSO-524? is a standardised lipid extract of the New Zealand green-lipped mussel and is an inflammatory modulator that inhibits the 5?-lipoxygenase and cyclooxygenase pathways and decreases concentrations of the pro-inflammatory arachidonic acid (AA). Methods PCSO-524? or a matched placebo was administered for 14?weeks to 144 parti...

  3. Double-blind, placebo controlled food challenge with apple

    DEFF Research Database (Denmark)

    Hansen, K.S.; Vestergaard, H.S.; Skov, P.S.

    2001-01-01

    The aim of the study was to develop and evaluate different methods of double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze-dried apple powder. All challenges were performed outside...... the pollen season and took place from 1997 to 1999. The freeze-dried apple material was characterized by means of leukocyte histamine release (HR), skin prick test (SPT), and immunoblotting experiments. The study population consisted of birch pollen-allergic patients with a history of rhinitis in the birch......-pollen season and positive specific IgE to birch. For comparison of the DBPCFC models, 65 patients with a positive open oral challenge with apple were selected. In the characterization of the freeze-dried apple material, 46 birch pollen-allergic patients were included. The IgE reactivity to apple was evaluated...

  4. Validation and acceptability of double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Venter, Carina; Maslin, Kate; Patil, Veeresh; Grundy, Jane; Glasbey, Gillian; Raza, Abid; Vlieg-Boerstra, Berber; Dean, Taraneh

    2016-01-01

    The Double Blind Placebo Controlled Food Challenge (DBPCFC) is considered the gold standard for food allergy diagnosis (1, 2). It is recommended that active and placebo challenge foods for DBPCFCs are sufficiently blinded in terms of smell, flavour and texture. Difficulties arise with children

  5. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

    Science.gov (United States)

    Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

    2014-01-01

    Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

  6. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

    Science.gov (United States)

    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were

  7. Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis : results of a multicentre, double-blind, randomised-withdrawal trial

    NARCIS (Netherlands)

    Brunner, Hermine I; Ruperto, Nicolino; Tzaribachev, Nikolay; Horneff, Gerd; Chasnyk, Vyacheslav G.; Panaviene, Violeta Vladislava; Abud-Mendoza, Carlos; Reiff, Andreas; Alexeeva, Ekaterina; Rubio-Pérez, Nadina; Keltsev, Vladimir; Kingsbury, Daniel J.; Del Rocio Maldonado Velázquez, Maria; Nikishina, Irina; Silverman, Earl D.; Joos, Rik; Smolewska, Elzbieta; Bandeira, Márcia; Minden, Kirsten; van Royen-Kerkhof, Annet; Emminger, Wolfgang; Foeldvari, Ivan; Lauwerys, Bernard R.; Sztajnbok, Flavio; Gilmer, Keith E.; Xu, Zhenhua; Leu, Jocelyn H.; Kim, Lilianne; Lamberth, Sarah L.; Loza, Matthew J.; Lovell, Daniel J.; Martini, Alberto

    2018-01-01

    OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received

  8. Weight Maintenance with Litramine (IQP-G-002AS: A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Barbara Grube

    2015-01-01

    Full Text Available Background. Litramine (IQP-G-002AS was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day or a matching placebo. Primary endpoints were difference of mean body weight (kg between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (-0.62±1.55 kg versus 1.62±1.48 kg, p<0.001. More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387.

  9. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

  10. Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold

    Directory of Open Access Journals (Sweden)

    Fazekas Tamas

    2012-09-01

    Full Text Available Abstract Background Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. Methods We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years, displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12% as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. Results The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038, reduction of viral load (p = 0.026, and lower incidence of secondary infections with other respiratory viruses (p = 0.046 indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. Conclusion In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. Trial registration ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

  11. Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold.

    Science.gov (United States)

    Fazekas, Tamas; Eickhoff, Philipp; Pruckner, Nathalie; Vollnhofer, Georg; Fischmeister, Gustav; Diakos, Christopher; Rauch, Margit; Verdianz, Maria; Zoubek, Andreas; Gadner, Helmut; Lion, Thomas

    2012-09-05

    Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1-18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2-7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

  12. PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Day Richard O

    2010-07-01

    Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

  13. Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

    Science.gov (United States)

    Schilling, J; Mueller, R S

    2012-07-28

    Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

  14. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

    DEFF Research Database (Denmark)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent

    2017-01-01

    BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from...... cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone....../day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis...

  15. An alternative approach to treating lateral epicondylitis. A randomized, placebo-controlled, double-blinded study

    NARCIS (Netherlands)

    Nourbakhsh, Mohammad Reza; Fearon, Frank J.

    Objective: To investigate the effect of noxious level electrical stimulation on pain, grip strength and functional abilities in subjects with chronic lateral epicondylitis. Design: Randomized, placebo-control, double-blinded study. Setting: Physical Therapy Department, North Georgia College and

  16. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

    2011-01-01

    o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,

  17. Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

    Science.gov (United States)

    Poewe, Werner; Seppi, Klaus; Fitzer-Attas, Cheryl J; Wenning, Gregor K; Gilman, Sid; Low, Phillip A; Giladi, Nir; Barone, Paolo; Sampaio, Cristina; Eyal, Eli; Rascol, Olivier

    2015-02-01

    Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic

  18. Flurbiprofen microgranules for relief of sore throat: a randomised, double-blind trial

    Science.gov (United States)

    Russo, Marc; Bloch, Mark; de Looze, Fred; Morris, Christopher; Shephard, Adrian

    2013-01-01

    Background Many people with sore throat seek, and are often inappropriately prescribed, antibiotics. Aim The objective of this study was to determine the analgesic efficacy of flurbiprofen 8.75 mg microgranules versus placebo. These microgranules are a possible alternative treatment for patients with sore throat due to upper respiratory tract infection (URTI). Design and setting Randomised, double-blind, placebo-controlled, multiple-dose study conducted at eight primary care sites in Australia. Method Participants with sore throat of onset within the past 4 days received either flurbiprofen 8.75 mg microgranules or non-medicated placebo microgranules. Throat soreness, difficulty in swallowing, sore throat pain intensity, sore throat relief, oral temperature, and treatment benefits were all assessed at regular intervals. Result Of 373 patients from eight centres, 186 received flurbiprofen 8.75 mg microgranules and 187 received placebo microgranules (intent-to-treat population). Throat soreness was significantly reduced over the first 2 hours after the first dose. Reductions in difficulty in swallowing were observed at all time points from 5 to 360 minutes after the first dose, after taking flurbiprofen microgranules versus placebo. Sore throat relief was also evident at 1 minute and lasted for at least 6 hours. The multiple-dose efficacy results showed reduction of difficulty in swallowing at the end of days 1–3 and sore throat relief at the end of day 1. Conclusion Microgranules containing flurbiprofen 8.75 mg provided fast and effective relief from sore throat due to URTI and represent an alternative treatment option to antibiotic therapy. PMID:23561694

  19. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease.

    Directory of Open Access Journals (Sweden)

    Mercè Rosinach

    Full Text Available The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS, which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.Double-blind randomized clinical trial of gluten vs placebo rechallenge.>18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day and 7 placebo. Clinical symptoms, quality of life (GIQLI, and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01. Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01. The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50% patients as having probable 'coeliac lite' disease.This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet.ClinicalTrials.gov NCT02472704.

  20. Effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial

    Science.gov (United States)

    Taavoni, Simin; Haghani, Hamid

    2017-01-01

    Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50–60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris, 12.27 mg of Zingiber officinale, 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum, while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms. PMID:28546803

  1. Effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Simin Taavoni

    2017-04-01

    Full Text Available Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50–60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris , 12.27 mg of Zingiber officinale, 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum, while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms.

  2. Effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial.

    Science.gov (United States)

    Taavoni, Simin; Ekbatani, Neda Nazem; Haghani, Hamid

    2017-03-01

    Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50-60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris , 12.27 mg of Zingiber officinale , 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum , while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms.

  3. Ultrasound guided injection of dexamethasone versus placebo for treatment of plantar fasciitis: protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Gilheany Mark F

    2010-07-01

    Full Text Available Abstract Background Plantar fasciitis is the most commonly reported cause of chronic pain beneath the heel. Management of this condition commonly involves the use of corticosteroid injection in cases where less invasive treatments have failed. However, despite widespread use, only two randomised trials have tested the effect of this treatment in comparison to placebo. These trials currently offer the best available evidence by which to guide clinical practice, though both were limited by methodological issues such as insufficient statistical power. Therefore, the aim of this randomised trial is to compare the effect of ultrasound-guided corticosteroid injection versus placebo for treatment of plantar fasciitis. Methods The trial will be conducted at the La Trobe University Podiatry Clinic and will recruit 80 community-dwelling participants. Diagnostic ultrasound will be used to diagnose plantar fasciitis and participants will be required to meet a range of selection criteria. Participants will be randomly allocated to one of two treatment arms: (i ultrasound-guided injection of the plantar fascia with 1 mL of 4 mg/mL dexamethasone sodium phosphate (experimental group, or (ii ultrasound-guided injection of the plantar fascia with 1 mL normal saline (control group. Blinding will be applied to participants and the investigator performing procedures, measuring outcomes and analysing data. Primary outcomes will be pain measured by the Foot Health Status Questionnaire and plantar fascia thickness measured by ultrasound at 4, 8 and 12 weeks. All data analyses will be conducted on an intention-to-treat basis. Conclusion This will be a randomised trial investigating the effect of dexamethasone injection on pre-specified treatment outcomes in people with plantar fasciitis. Within the parameters of this protocol, the trial findings will be used to make evidence-based recommendations regarding the use of corticosteroid injection for treatment of this

  4. IPARZINE-SKR study: randomized, double-blind clinical trial of a new topical product versus placebo to prevent pressure ulcers.

    Science.gov (United States)

    Verdú, José; Soldevilla, Javier

    2012-10-01

    This study compared the efficacy of a new topical agent (IPARZINE-4A-SKR) on preventing category I pressure ulcers (PUs) over a 2-week period, compared with a placebo. A double-blind, randomised, multi-centre, placebo-controlled clinical trial in two parallel groups was conducted. The primary objective was to compare PU incidence between groups. Hospital and socio-sanitary centre patients (n = 194) at risk of developing a PU (Braden scale) were randomised into two groups. The intervention group included 99 patients, and the placebo group comprised 95 patients. Patients were comparable in terms of age, sex and PU risk. In both groups, patients had a high risk of developing PUs. The product was applied on the sacrum, trochanters and heels. Six PUs (incidence = 6·1%) were detected in the intervention group versus seven (incidence = 7·4%) in the placebo group. Differences were not statistically significant (z = 0·08; P = 0·94), relative risk = 0·82 (95% confidence interval = 0·29–2·36). The main limitation of the study was the sample size and, therefore, the main difficulty encountered was in determining whether the product is ineffective or simply has not been used with sufficient patients. In conclusion, it is not possible to confirm that there are any differences between the studied and the placebo treatments in the prevention of PUs. The results obtained were similar to those obtained in studies of PU prevention using products based on topical fatty acids.

  5. Double-blind clonazepam vs placebo in panic disorder treatment

    Directory of Open Access Journals (Sweden)

    VALENÇA ALEXANDRE MARTINS

    2000-01-01

    Full Text Available OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day, compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1% were free of panic attacks, compared with 8 of 13 (61.5% clonazepam patients (Fisher exact test; p=0,031. CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.

  6. Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

    Science.gov (United States)

    Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

    2013-08-01

    Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

  7. Published and not fully published double-blind, randomised, controlled trials with oral naratriptan in the treatment of migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer Carsten

    2011-01-01

    Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs are publi......Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs...... are published in full. Naratriptan 2.5 mg is superior to placebo for acute migraine treatment in 6 RCTs, but inferior to sumatriptan 100 mg and rizatriptan 10 mg in one RCT each. This dose of naratriptan has no more adverse events than placebo. Naratriptan 1 mg b.i.d. has some effect in the short...

  8. Efficacy of Intravenous Haloperidol on the duration of Delirium and Coma in Critically Ill Patients (Hope-ICU): a Randomised, Placebo-Controlled Trial

    Science.gov (United States)

    Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

    2016-01-01

    Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0

  9. "Live high-train low" using normobaric hypoxia: a double-blinded, placebo-controlled study

    DEFF Research Database (Denmark)

    Siebenmann, Christoph; Robach, Paul; Jacobs, Robert A

    2012-01-01

    The combination of living at altitude and training near sea level [live high-train low (LHTL)] may improve performance of endurance athletes. However, to date, no study can rule out a potential placebo effect as at least part of the explanation, especially for performance measures. With the use o...... of a placebo-controlled, double-blinded design, we tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Sixteen endurance cyclists trained for 8 wk at low altitude (...

  10. Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study.

    Science.gov (United States)

    Oelke, Matthias; Giuliano, François; Baygani, Simin K; Melby, Thomas; Sontag, Angelina

    2014-10-01

    To assess treatment satisfaction with tadalafil or tamsulosin vs placebo in a 12-week, randomised, double-blind study of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). After a 4-week placebo lead-in period, men aged ≥45 years with an International Prostate Symptom Score (IPSS) of ≥13 and a maximum urinary flow rate of ≥4 to ≤15 mL/s received placebo (172 men), tadalafil 5 mg (171), or tamsulosin 0.4 mg (168) once daily for 12 weeks. Treatment Satisfaction Scale-BPH (TSS-BPH) responses were assessed based on median treatment differences using the van Elteren test. Overall treatment satisfaction was greater for tadalafil vs placebo (P = 0.005), based on greater satisfaction with efficacy (P = 0.003); neither overall treatment satisfaction nor satisfaction with efficacy was greater for tamsulosin vs placebo (P ≥ 0.409). For individual questions, 66.5% of men rated tadalafil treatment as 'effective/very effective' (Question 1, Q1) vs placebo (P = 0.011), 72.6% would 'definitely/probably recommend their treatment' (Q3; P = 0.043), 71.8% were generally 'very satisfied/satisfied with their medication' (Q8; P BPH by baseline age (≤65/>65 years), history of erectile dysfunction (yes/no), LUTS/BPH severity (IPSSplacebo, with only borderline difference for men without prior therapy. Treatment satisfaction was greater with tadalafil vs placebo, with no significant difference between tamsulosin and placebo. © 2014 The Authors. BJU International © 2014 BJU International.

  11. Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

    Science.gov (United States)

    Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

    2016-06-01

    Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

  12. Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

    Science.gov (United States)

    Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

    2017-09-01

    Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

  13. RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    De Soyza, Anthony; Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

    2018-01-01

    We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and pre-defined bacteria in sputum.In this phase III, double-blind, placebo-controlled trial, patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in two treatment regimens consisting of on/off treatment cycles of 14 or 28 days for 48 weeks. The primary end-points were time to first exacerbation and frequency of exacerbations.A total of 416 patients were randomised to the 14-day on/off regimen (ciprofloxacin DPI (n=137) and placebo (n=68)) or the 28-day on/off regimen (ciprofloxacin DPI (n=141) and placebo (n=70)). Ciprofloxacin DPI 14 days on/off significantly prolonged time to first exacerbation versus pooled placebo (median time >336 versus 186 days; hazard ratio 0.53, 97.5% CI 0.36-0.80; p=0.0005) and reduced the frequency of exacerbations compared with matching placebo by 39% (mean number of exacerbations 0.6 versus 1.0; incidence rate ratio 0.61, 97.5% CI 0.40-0.91; p=0.0061). Outcomes for ciprofloxacin DPI 28 days on/off were not statistically significantly different from placebo. The safety profile of ciprofloxacin DPI was favourable.Ciprofloxacin DPI was well tolerated and has the potential to be an effective treatment option in non-cystic fibrosis bronchiectasis. Copyright ©ERS 2018.

  14. New validated recipes for double-blind placebo-controlled low-dose food challenges.

    Science.gov (United States)

    Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

    2013-05-01

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  15. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

    DEFF Research Database (Denmark)

    Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

    2010-01-01

    This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

  16. The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

    2017-07-01

    The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

  17. No matrix effect in double-blind, placebo-controlled egg challenges in egg allergic children

    NARCIS (Netherlands)

    Libbers, L.; Flokstra-de Blok, B. M. J.; Vlieg-Boerstra, B. J.; van der Heide, S.; van der Meulen, G. N.; Kukler, J.; Kerkhof, M.; Dubois, A. E. J.

    Background Diagnostic and accidental food allergic reactions may be modified by the matrix containing the allergenic food. Previous studies of double-blind, placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the fat content of the challenge matrix on the severity of the

  18. A double-blind placebo controlled trial of paroxetine in the ...

    African Journals Online (AJOL)

    A double-blind placebo controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa. Dan J. Stein, Michael Berk, Charl Els, Robin A. Emsley, Leon Gittelson, Don Wilson, Rosemary Oakes, Brian Hunter ...

  19. Exclusively breastfed infants at risk for false negative double blind placebo controlled milk challenge

    NARCIS (Netherlands)

    Petrus, N. C. M.; Kole, E. A.; Schoemaker, A. A.; van Aalderen, W. M. C.; Sprikkelman, A. B.

    2014-01-01

    The double blind placebo controlled food challenge (DBPCFC) is the gold standard for diagnosing cow's milk allergy (CMA). However, false-negative DBPCFC have been reported. We present 2 cases with a false negative DBPCFC in exclusively breastfed infants suspected of CMA. These cases highlight the

  20. A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence.

    LENUS (Irish Health Repository)

    Farren, Conor K

    2009-01-01

    Significant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone would be augmented by concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI).

  1. Clinical effects of buspirone in social phobia : A double-blind placebo-controlled study

    NARCIS (Netherlands)

    denBoer, JA; Westenberg, HGM; Pian, KLH

    Background: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. Method: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled

  2. Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study

    NARCIS (Netherlands)

    Nosten, F.; ter Kuile, F.; Maelankiri, L.; Chongsuphajaisiddhi, T.; Nopdonrattakoon, L.; Tangkitchot, S.; Boudreau, E.; Bunnag, D.; White, N. J.

    1994-01-01

    A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI],

  3. ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study

    NARCIS (Netherlands)

    Lansbergen, M.M.; Dongen-Boomsma, M. van; Buitelaar, J.K.; Slaats-Willemse, D.I.E.

    2011-01-01

    Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo

  4. A double-blind comparison of fluvoxamine versus placebo in the treatment of compulsive buying disorder.

    Science.gov (United States)

    Black, D W; Gabel, J; Hansen, J; Schlosser, S

    2000-12-01

    Nondepressed outpatients with a compulsive buying disorder were recruited by advertisement and word of mouth for inclusion in a controlled treatment trial. Following a 1-week single-blind placebo washout, subjects were randomly assigned to fluvoxamine (n = 12) or placebo (n = 11). Subjects received fluvoxamine (up to 300 mg daily) or placebo for 9 weeks. There were few dropouts. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale--Shopping Version (YBOCS-SV), three Clinical Global Impressions (CGI) ratings, the Hamilton Rating Scale for Depression (HRSD), and the Maudsley Obsessive-compulsive Inventory (MOI). At the conclusion of the trial, 50% of fluvoxamine recipients and 63.6% of placebo recipients achieved CGI ratings of "much" or "very much" improvement, while 33% of fluvoxamine recipients were "very much" improved compared with 18% of placebo recipients (by endpoint analysis). Subjects in both treatment cells showed improvement as early as the second week of the trial, and for most, improvement continued during the 9-week study. There were no significant differences between fluvoxamine- and placebo-treated subjects on any of the outcome measures, with the exception that fluvoxamine recipients achieved greater improvement than placebo recipients on the MOI (p = .02). Adverse experiences were more frequent in the group receiving fluvoxamine, particularly nausea, insomnia, decreased motivation, and sedation. We conclude that in a short-term treatment trial of compulsive buying, subjects receiving fluvoxamine or placebo respond similarly.

  5. The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial.

    Science.gov (United States)

    Neerland, Bjørn Erik; Hov, Karen Roksund; Bruun Wyller, Vegard; Qvigstad, Eirik; Skovlund, Eva; MacLullich, Alasdair M J; Bruun Wyller, Torgeir

    2015-02-10

    Delirium affects 15% of hospitalised patients and is linked with poor outcomes, yet few pharmacological treatment options exist. One hypothesis is that delirium may in part result from exaggerated and/or prolonged stress responses. Dexmedetomidine, a parenterally-administered alpha2-adrenergic receptor agonist which attenuates sympathetic nervous system activity, shows promise as treatment in ICU delirium. Clonidine exhibits similar pharmacodynamic properties and can be administered orally. We therefore wish to explore possible effects of clonidine upon the duration and severity of delirium in general medical inpatients. The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is a randomised, placebo-controlled, double-blinded, parallel group study with 4-month prospective follow-up. We will recruit 100 older medical inpatients with delirium or subsyndromal delirium in the acute geriatric ward. Participants will be randomised to oral clonidine or placebo until delirium free for 2 days (Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria), or after a maximum of 7 days treatment. Assessment of haemodynamics (blood pressure, heart rate and electrocardiogram) and delirium will be performed daily until discharge or a maximum of 7 days after end of treatment. The primary endpoint is the trajectory of delirium over time (measured by Memorial Delirium Assessment Scale). Secondary endpoints include the duration of delirium, use of rescue medication for delirium, pharmacokinetics and pharmacodynamics of clonidine, cognitive function after 4 months, length of hospital stay and need for institutionalisation. LUCID will explore the efficacy and safety of clonidine for delirium in older medical inpatients. ClinicalTrials.gov NCT01956604. EudraCT Number: 2013-000815-26.

  6. Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Forbes Andrew

    2010-10-01

    Full Text Available Abstract Background Hip osteoarthritis (OA is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044

  7. Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

    Science.gov (United States)

    2010-01-01

    Background Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044 PMID:20946621

  8. Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

    Science.gov (United States)

    Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Nobuko; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kanouchi, Tadashi; Kohara, Nobuo; Kawamoto, Michi; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Hirata, Koichi; Kokubun, Norito; Masuda, Ray; Kaneko, Juntaro; Yabe, Ichiro; Sasaki, Hidenao; Kaida, Ken-Ichi; Takazaki, Hiroshi; Suzuki, Norihiro; Suzuki, Shigeaki; Nodera, Hiroyuki; Matsui, Naoko; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu

    2018-06-01

    Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression

  9. A natural seaweed derived mineral supplement (Aquamin F for knee osteoarthritis: A randomised, placebo controlled pilot study

    Directory of Open Access Journals (Sweden)

    Kuskowski Michael A

    2009-02-01

    Full Text Available Abstract Background Osteoarthritis (OA is a slowly destructive process that may be influenced by a nutritional mineral balance in the body. Methods This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin on 6 minute walking distance (6 MWD, range of motion (ROM, and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs that were being used daily for pain management. Subjects (n = 29 with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d or Placebo for up to 12 weeks. Results Of the 29 subjects initially randomized, only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline. Fourteen subjects completed the study and an ITT analysis (n = 22 of the data showed no significant differences in WOMAC scores however, the data did reveal significant improvements in passive and active extension ROM (0.83° ± 1.54 vs. -1.54° ± 2.43; difference, 5.2° ± 2.2, p = 0.028 and 6 MWD (150 ± 48 ft vs. 12.5 ± 31.5 ft; difference, 136 ± 57 ft, p = 0.03 in the Aquamin group compared to the placebo group; respectively, following a 50% reduction in NSAID use. The treatments were well tolerated and the adverse event profiles were not significantly different between the groups. Conclusion This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment. Additional research is needed to confirm these preliminary observations. Trial registration NCT00755482

  10. The effect of escitalopram versus placebo on perceived stress and salivary cortisol in healthy first-degree relatives of patients with depression-A randomised trial

    DEFF Research Database (Denmark)

    Knorr, Ulla; Vinberg, Maj; Gether, Ulrik

    2012-01-01

    The effect of selective serotonin reuptake inhibitors (SSRI) on healthy individuals remains unclear. We tested the hypothesis that escitalopram decreases perceived stress and salivary cortisol. The trial has a randomised, blinded, placebo-controlled, parallel-group design. After informed consent 80...... intervals for the next hour, and at 12:00, 18:00 and 23:00. The salivary cortisol awakening response, all day salivary cortisol, and scale scores on sleep, pain, aggression, quality of life, and perceived stress assessed at entry were compared to values following 4 weeks of intervention. Statistically...... significant decreases were found in awakening salivary cortisol (P=0.04) and in all day salivary cortisol (P=0.02) in the escitalopram group compared with the placebo group. There were no statistically significant differences in perceived stress between the intervention groups. These findings from...

  11. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

    DEFF Research Database (Denmark)

    Chaturvedi, N.; Porta, M.; Klein, R.

    2008-01-01

    of retinopathy in type 1 diabetes. METHODS: Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing...... retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After 1 month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression......BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression...

  12. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double-blind randomised controlled trial.

    Science.gov (United States)

    Bellad, M B; Tara, D; Ganachari, M S; Mallapur, M D; Goudar, S S; Kodkany, B S; Sloan, N L; Derman, R

    2012-07-01

    Sublingual misoprostol produces a rapid peak concentration, and is more effective than oral administration. We compared the postpartum measured blood loss with 400 μg powdered sublingual misoprostol and after standard care using 10 iu intramuscular (IM) oxytocin. Double-blind randomised controlled trial. A teaching hospital: J N Medical College, Belgaum, India. A cohort of 652 consenting eligible pregnant women admitted to the labour room. Subjects were assigned to receive the study medications and placebos within 1 minute of clamping and cutting the cord by computer-generated randomisation. Chi-square and bootstrapped Student's t-tests were used to test categorical and continuous outcomes, respectively. Measured mean postpartum blood loss and haemorrhage (PPH, loss ≥ 500 ml), >10% pre- to post-partum decline in haemoglobin, and reported side effects. The mean blood loss with sublingual misoprostol was 192 ± 124 ml (n=321) and 366 ± 136 ml with oxytocin IM (n=331, P ≤ 0.001). The incidence of PPH was 3.1% with misoprostol and 9.1% with oxytocin (P=0.002). No woman lost ≥ 1000 ml of blood. We observed that 9.7% and 45.6% of women experienced a haemoglobin decline of >10% after receiving misoprostol and oxytocin, respectively (P ≤ 0.001). Side effects were significantly greater in the misoprostol group than in the oxytocin group. Unlike other studies, this trial found sublingual misoprostol more effective than intramuscular oxytocin in reducing PPH, with only transient side effects being greater in the misoprostol group. The sublingual mode and/or powdered formulation may increase the effectiveness of misoprostol, and render it superior to injectable oxytocin for the prevention of PPH. Further research is needed to confirm these results. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

  13. Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

    Science.gov (United States)

    Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

    2006-08-01

    Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

  14. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; Herpertz, I.; Pasker, L.; van der Heide, S.; Kukler, J.; Jansink, C.; Vaessen, W.; Beusekamp, B. J.; Dubois, A. E. J.

    P>Background: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of

  15. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; Herpertz, I.; Pasker, L.; van der Heide, S.; Kukler, J.; Jansink, C.; Vaessen, W.; Beusekamp, B. J.; Dubois, A. E. J.

    2011-01-01

    In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for

  16. Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.

    Science.gov (United States)

    Moore, R Andrew; Gay-Escoda, C; Figueiredo, R; Tóth-Bagi, Z; Dietrich, T; Milleri, S; Torres-Lagares, D; Hill, C M; García-García, A; Coulthard, P; Wojtowicz, A; Matenko, D; Peñarrocha-Diago, M; Cuadripani, S; Pizà-Vallespir, B; Guerrero-Bayón, C; Bertolotti, M; Contini, M P; Scartoni, S; Nizzardo, A; Capriati, A; Maggi, C A

    2015-01-01

    Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

  17. Total hip arthroplasty and perioperative oral carbohydrate treatment: a randomised, double-blind, controlled trial.

    Science.gov (United States)

    Harsten, Andreas; Hjartarson, Hjörtur; Toksvig-Larsen, Sören

    2012-06-01

    Perioperative oral carbohydrate intake is beneficial to general surgery patients. Total hip arthroplasty is a common surgical procedure, and even a moderate improvement in patient outcome could have a significant effect on the resources needed for these patients. However, few studies have focused on the effects of carbohydrate intake on orthopaedic patients. The purpose of this study was to investigate if perioperative oral carbohydrate intake alters the postoperative course for patients undergoing total hip arthroplasty. The primary hypothesis was that pain scores would be lower in patients treated with carbohydrate. A randomised, double-blind, controlled trial. This study was carried out between September 2009 and April 2011 at a district Swedish hospital that specialises in orthopaedic surgery. Sixty ASA physical status I-III patients scheduled for elective total hip arthroplasty were included. Exclusion criteria were obesity, diabetes, prior hip surgery to the same hip, ongoing infection, immunological deficiency or age less than 50 or more than 80 years. Patients were given 400 ml of either an oral 12.5% carbohydrate solution or a placebo beverage (flavoured water) 1.5 h before and 2 h after surgery. Visual analogue scales were used to score six discomfort parameters. Immediately prior to surgery, the carbohydrate-treated patients were less hungry (median score 9.5 vs. 22 mm) and experienced less nausea (0 vs. 1.5 mm) (Phip arthroplasty.

  18. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    OpenAIRE

    Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

    1985-01-01

    The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

  19. A double-blind comparison of clebopride and placebo in dyspepsia secondary to delayed gastric emptying.

    Science.gov (United States)

    Bavestrello, L; Caimi, L; Barbera, A

    1985-01-01

    Seventy-six patients suffering from dyspeptic symptoms secondary to roentgenologically demonstrated delayed gastric emptying were treated with clebopride (0.5 mg TID) or with placebo during a three-month double-blind trial. Clebopride was more effective (P less than or equal to 0.001) than placebo in reducing or relieving symptoms and roentgenological findings associated with delayed gastric emptying. No interactions of clebopride with concomitant drugs or coexisting disorders were observed, and the incidence of side effects was low. We conclude that clebopride will be beneficial in the management of patients with delayed gastric emptying.

  20. Effect of the laxative magnesium oxide on gastrointestinal functional recovery in fast-track colonic resection: a double-blind, placebo-controlled randomized study

    DEFF Research Database (Denmark)

    Andersen, J; Christensen, H; Pachler, J H

    2012-01-01

    Aim: A double-blind randomised controlled study was conducted to compare the effect of magnesium oxide (1 g 12-hourly) with placebo given within an evidence-based multimodal rehabilitation programme on gastrointestinal recovery, pain, mobilisation and hospital stay after open colonic resection....... Method: Of sixty two potentially eligible patients, thirteen were excluded leaving 22 in the magnesium oxide group and 27 in the placebo group. The main outcome measure was time to normalization of bowel function. Secondary outcome measures included post operative nausea, vomiting, pain, fatigue...... were similar in the groups (p>0.3). The median postoperative hospital stay was three days in both groups (p>0.65). Conclusion: Magnesium oxide does not enhance the recovery of gastrointestinal function within the context of an evidence-based multimodal rehabilitation programme after open colonic...

  1. Immediate effects of microsystem acupuncture in patients with oromyofacial pain and craniomandibular disorders (CMD): a double-blind, placebo-controlled trial.

    Science.gov (United States)

    Simma, I; Gleditsch, J M; Simma, L; Piehslinger, E

    2009-12-19

    Patients presenting with oromyofacial disorders and pain in the head and neck area are often resistant to conventional therapy. Acupuncture has been shown to be effective in pain reduction. Twenty-three patients with craniomandibular disorders, headache and, in particular, local pain in the orofacial, cervical and temporomandibular joint areas were randomised into acupuncture or placebo laser therapy groups. Pain was assessed by a visual analogue scale (VAS) and by palpation of 14 muscles and groups of muscles immediately before and after treatment, the assessor being blinded to the patients' allocation. Applicable acupuncture points were searched and pricked using the 'very-point' technique. Pain reduction measured by VAS was significantly more pronounced after acupuncture than after placebo treatment (p=0.031). Sum of pain scores across 14 muscles was considerably more reduced after acupuncture as compared to sham laser treatment. Acupuncture may bring about immediate pain relief in patients with oromyofacial disorders, increasing the chance to initiate other therapeutic measures.

  2. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.

    Science.gov (United States)

    Norman, Jane Elizabeth; Marlow, Neil; Messow, Claudia-Martina; Shennan, Andrew; Bennett, Phillip R; Thornton, Steven; Robson, Stephen C; McConnachie, Alex; Petrou, Stavros; Sebire, Neil J; Lavender, Tina; Whyte, Sonia; Norrie, John

    2016-05-21

    Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373. Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes

  3. The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Li Li

    2010-05-01

    Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

  4. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

    Science.gov (United States)

    Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

    2015-03-01

    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

  5. A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

    Science.gov (United States)

    Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

    2007-02-01

    This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

  6. Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial

    DEFF Research Database (Denmark)

    Springborg, J B; Møller, C; Gideon, P

    2007-01-01

    but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i...

  7. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study.

    Science.gov (United States)

    Scheidtmann, K; Fries, W; Müller, F; Koenig, E

    2001-09-08

    Functional disability is generally caused by hemiplegia after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia. We did a prospective, randomised, placebo-controlled, double-blind study in which we enrolled 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. We quantitatively assessed motor function every week with Rivermead motor assessment (RMA). Six patients were excluded from analyses because of non-neurological complications. Motor recovery was significantly improved after 3 weeks of drug intervention in those on levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment (pstroke rehabilitation.

  8. Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

    Science.gov (United States)

    Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

    2017-02-03

    Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

  9. Aspartame sensitivity? A double blind randomised crossover study.

    Directory of Open Access Journals (Sweden)

    Thozhukat Sathyapalan

    Full Text Available Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation.This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics.Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008 and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04, reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects.Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that

  10. Aspartame sensitivity? A double blind randomised crossover study.

    Science.gov (United States)

    Sathyapalan, Thozhukat; Thatcher, Natalie J; Hammersley, Richard; Rigby, Alan S; Courts, Fraser L; Pechlivanis, Alexandros; Gooderham, Nigel J; Holmes, Elaine; le Roux, Carel W; Atkin, Stephen L

    2015-01-01

    Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of

  11. Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

    Science.gov (United States)

    Kahaly, George J; Riedl, Michaela; König, Jochem; Diana, Tanja; Schomburg, Lutz

    2017-11-01

    Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD. Copyright © 2017 Endocrine Society

  12. Femicomfort in the Treatment of Premenstrual Syndromes: A Double-Blind, Randomized and Placebo Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2010-06-01

    Full Text Available "nObjective:Premenstrual syndromes (PMS affecting 20-40% of women of reproductive age. The aim of this double blind and placebo controlled trial was to investigate whether femicofort a supplement contains Vitamin B6, Vitamin E and evening primrose oil could relieve symptoms of PMS. "nMethod: This was a randomized and double blind clinical trial. The trial was conducted between November 2009 and April March 2010. Women aged 20 to 45 years with regular menstrual cycles and experience of PMS symptoms (According to the current diagnostic criteria proposed by the American College of Obstetrics and Gynecology for at least 6 months were eligible for the study. Patients were randomized to receive femicomfort or placebo in a 1: ratio using a computer-generated code. The assignments were kept in sealed, opaque envelopes until the point of analysis of data. In this double-blind, patients were randomly assigned to receive capsule of femicomfort (Group A or capsule placebo for two menstrual cycles (cycles 3 and 4. The primary outcome measure was the Daily Symptom Report, a checklist of 17 premenstrual symptoms rated from 0 to 4 according to their severity throughout the menstrual cycle. Secondary outcome measure was Hamilton Depression Rating Scale (17-item. "nResults:Femicomfort at this dose was found to be effective in relieving symptoms of PMS. The difference between the femicomfort and placebo in the frequency of side effects was not significant. Conclusion: The results of this study indicate the efficacy of femicomfort in the treatment of PMS.

  13. Randomised clinical trial: the clinical efficacy and safety of an alginate-antacid (Gaviscon Double Action) versus placebo, for decreasing upper gastrointestinal symptoms in symptomatic gastroesophageal reflux disease (GERD) in China.

    Science.gov (United States)

    Sun, J; Yang, C; Zhao, H; Zheng, P; Wilkinson, J; Ng, B; Yuan, Y

    2015-10-01

    There is a paucity of large-scale studies evaluating the clinical benefit of the Gaviscon Double Action (DA) alginate-antacid formulation for treating gastroesophageal reflux disease (GERD) symptoms. Randomised double-blind placebo-controlled parallel-group study to evaluate efficacy and safety of Gaviscon DA in reducing heartburn, regurgitation and dyspepsia symptoms in individuals with mild-to-moderate GERD in China. Participants with symptomatic GERD (n = 1107) were randomised to receive Gaviscon DA or placebo (two tablets four times daily) for seven consecutive days. The primary endpoint compared the change in Reflux Disease Questionnaire (RDQ) score for the GERD (heartburn + regurgitation) dimension between Gaviscon DA and placebo. Secondary endpoints compared the change in RDQ scores for individual heartburn, regurgitation and dyspepsia dimensions, overall treatment evaluation (OTE) scores and incidence of adverse events (AEs). Mean RDQ GERD scores: 2.51 for Gaviscon DA and 2.50 for placebo at baseline; 1.25 for Gaviscon DA and 1.46 for placebo post treatment. Gaviscon DA was statistically superior to placebo in reducing GERD and dyspepsia RDQ scores [least-squares mean (LSM) difference: GERD -0.21, P GERD symptoms was observed both in those with non-erosive and those with erosive reflux disease (LSM difference -0.14 [P = 0.038] and -0.29 [P GERD. ClinicalTrials.gov: NCT01869491. © 2015 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

  14. Exploratory double-blind, parallel-group, placebo-controlled extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    2017-10-01

    Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer-term efficacy and safety. Patients given edaravone in the first 24-week phase III study (Cycles 1-6) were randomised to edaravone (E-E) or placebo (E-P) in the subsequent 24-week double-blind period (Cycles 7-12). Patients given placebo in phase III were switched to edaravone (P-E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13-15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy-expected subpopulation (EESP) defined by post-hoc analysis of the first phase III study. The least-squares mean and standard error of the intergroup difference (E-E vs. E-P) of change in the ALSFRS-R score from Cycles 7-12 was 1.16 ± 0.93 (p = 0.2176) in the FAS, and 1.85 ± 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E-E group throughout Cycles 1-15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E-E than in E-P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.

  15. Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris

    NARCIS (Netherlands)

    Gobel, EJAM; Hautvast, RWM; vanGilst, WH; Spanjaard, JN; Hillege, HL; DeJongste, MJL; Molhoek, GP; Lie, KI

    1995-01-01

    The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non- dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate. both given intravenously, in 129

  16. Unilateral pallidotomy in Parkinson's disease : a randomised, single-blind, multicentre trial

    NARCIS (Netherlands)

    de Bie, RMA; de Haan, RJ; Nijssen, PCG; Rutgers, AWF; Beute, GN; Haaxma, R; Schmand, B; Staal, MJ; Speelman, J.D.

    1999-01-01

    Background The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial. Methods We enrolled 37 patients with advanced

  17. Double blind, placebo-controlled trial of Tranexamic acid on recent internal hemorrhoid bleeding

    Directory of Open Access Journals (Sweden)

    Abdul A. Rani

    2002-12-01

    Full Text Available Double blind randomized placebo controlled trial was conducted to evaluate the efficacy of Tranexamic acid in 54 patients with recent hemorrhoid bleeding. Age, gender, body weight, height, grade of hemorrhoid, time of onset of recent bleeding were comparable between two groups. Analysis of haemostatic effect or stop bleeding as an immediate outcome of this study revealed that in the grade 2 patients, 23/23 (100% of tranexamic group and 18/23(78.26% of placebo group the bleeding stop. After 3 days of observation, there was statistically significant different for the rate of stop bleeding as well as at the end of observation. Bleeding stop earlier in the Tranexamic group with median 4 days (3-5 days, compare to placebo, median 11(9.55-12.45. Analysis of recurrent bleeding as an outcome of this study revealed that in the placebo group 9/18(50% of grade 2 patients and all grade 3 (100%patients suffered from recurrent bleeding. Since the days 4, both group have significant different time for recurrent bleeding and at the end of observation, cumulative probability of free of bleeding between two groups significantly different. Median still stop bleeding in the placebo group was 36 days, and the tranexamic group never reaches the median until the end of observation. Conclusion: tranexamic acid was an effective drug to stop recent hemorrhoid bleeding and prevent further recurrent bleeding, significantly better than placebo. (Med J Indones 2002;11: 215-21Keywords: Tranexamic acid, hemorrhoid bleeding, haemostatic effect, recurrent bleeding.

  18. Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial.

    Science.gov (United States)

    Furyk, Jeremy S; Chu, Kevin; Banks, Colin; Greenslade, Jaimi; Keijzers, Gerben; Thom, Ogilvie; Torpie, Tom; Dux, Carl; Narula, Rajan

    2016-01-01

    We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  19. Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

    Science.gov (United States)

    Wong, Eliza L Y; Sung, Rita Yn Tz; Leung, Ting Fan; Wong, Yeuk Oi; Li, Albert M C; Cheung, Kam Lau; Wong, Chun Kwok; Fok, Tai Fai; Leung, Ping Chung

    2009-10-01

    The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

  20. Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Tania Cursino de Menezes Couceiro

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

  1. Postoperative symbiotic in patients with head and neck cancer: a double-blind randomised trial.

    Science.gov (United States)

    Lages, Priscilla C; Generoso, Simone V; Correia, Maria Isabel T D

    2018-01-01

    Studies on the 'gut origin of sepsis' have suggested that stressful insults, such as surgery, can affect intestinal permeability, leading to bacterial translocation. Symbiotics have been reported to be able to improve gut permeability and modulate the immunologic system, thereby decreasing postoperative complications. Therefore we aimed to evaluate the postoperative use of symbiotics in head and neck cancer surgical patients for intestinal function and permeability, as well as the postoperative outcomes. Patients were double-blind randomised into the symbiotic (n 18) or the control group (n 18). Samples were administered twice a day by nasoenteric tube, starting on the 1st postoperative day until the 5th to 7th day, and comprised 109 colony-forming units/ml each of Lactobacillus paracasei, L. rhamnosus, L. acidophilus, and Bifidobacterium lactis plus 6 g of fructo-oligosaccharides, or a placebo (6 g of maltodextrin). Intestinal function (day of first evacuation, total stool episodes, stool consistency, gastrointestinal tract symptoms and gut permeability by diamine oxidase (DAO) enzyme) and postoperative complications (infectious and non-infectious) were assessed. Results of comparison of the pre- and postoperative periods showed that the groups were similar for all outcome variables. In all, twelve patients had complications in the symbiotic group v. nine in the control group (P>0·05), and the preoperative-postoperative DAO activity ranged from 28·5 (sd 15·4) to 32·7 (sd 11·0) ng/ml in the symbiotic group and 35·2 (sd 17·7) to 34·1 (sd 12·0) ng/ml in the control group (P>0·05). In conclusion, postoperative symbiotics did not impact on intestinal function and postoperative outcomes of head and neck surgical patients.

  2. Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA: A randomised placebo-controlled crossover trial

    Directory of Open Access Journals (Sweden)

    Richmond Stewart J

    2008-09-01

    Full Text Available Abstract Background Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. Methods/Design The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual

  3. Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture

    Directory of Open Access Journals (Sweden)

    Soyeon Cheon

    2018-01-01

    Full Text Available Abstract Background While full disclosure of information on placebo control in participant information leaflets (PILs in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. Methods Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. Results In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI −0.21 vs. −0.16; p = 0.38. In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference − 0.43 vs. −0.12; p = 0.03, probably due to enhanced expectations. Conclusions How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we

  4. A phase III double-blind randomised study of rectal sucralfate suspension in the prevention of acute radiation proctitis

    International Nuclear Information System (INIS)

    O'Brien, Peter C.; Franklin, C. Ian; Dear, Keith B.G.; Hamilton, Christopher C.; Poulsen, Michael; Joseph, David J.; Spry, Nigel; Denham, James W.

    1997-01-01

    Background and purpose: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. Materials and methods: Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. Results: There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 ± 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 ± 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. Conclusion: This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late

  5. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

    Science.gov (United States)

    Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

    2016-05-23

    Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

  6. Double-blind placebo-controlled pilot study of paroxetine for specific phobia.

    Science.gov (United States)

    Benjamin, J; Ben-Zion, I Z; Karbofsky, E; Dannon, P

    2000-04-01

    Drugs are not recognized as a standard treatment for specific phobia, despite its apparent similarities to other kinds of phobia. Reluctance on the part of patients and clinicians to see the disorder as more than normal anxiety may explain the apparent resistance to pharmacotherapy. Eleven patients fulfilling DSM-IV criteria for specific phobia were randomized to 4 weeks of double-blind treatment with placebo or paroxetine up to 20 mg/day. They were assessed weekly with the Fear Questionnaire and the Hamilton Rating Scale for Anxiety. Paroxetine showed significant superiority in reducing all measures (ANCOVA for reductions in phobia scores F=7.9, P=0.02). One out of six patients responded to placebo, compared to three out of five patients on paroxetine. This new therapeutic option (i.e. drug treatment) for specific phobia deserves further examination in a larger trial.

  7. Does granisetron eliminate the gag reflex? A crossover, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Barenboim, Silvina Friedlander; Dvoyris, Vladislav; Kaufman, Eliezer

    2009-01-01

    Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, double-blind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P = .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect.

  8. Pregabalin for anxiety in patients with schizophrenia - A randomized, double-blind placebo-controlled study

    DEFF Research Database (Denmark)

    Schjerning, Ole; Damkier, Per; Lykkegaard, Signe Engelhardt

    2017-01-01

    INTRODUCTION: Anxiety is frequent in patients with schizophrenia and poses a major impact on patients perceived quality of life, daily functioning and risk of suicide. Pregabalin has shown effective in the treatment of generalized anxiety disorder and has been suggested for the treatment of anxiety...... in patients with schizophrenia. As evidence is sparse regarding treatment of anxiety in this patient group, we aimed to investigate the use of pregabalin for anxiety in patients with schizophrenia. METHODS: A randomized, double-blind placebo controlled study was used. Patients were randomized to either...... placebo or pregabalin (≤600mg/d) as add-on treatment. Primary analyses were intention-to-treat based with change in Hamilton Anxiety Scale after 4 and 8weeks of treatment as primary outcome. Secondary outcomes were change in psychopathology, quality-of-life, cognitive functioning and sleep. The study used...

  9. Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

    Science.gov (United States)

    Reimer, C; Lødrup, A B; Smith, G; Wilkinson, J; Bytzer, P

    2016-04-01

    Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21). © 2016 John Wiley & Sons Ltd.

  10. Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia.

    Science.gov (United States)

    Schabus, Manuel; Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P J; Wislowska, Malgorzata; Hoedlmoser, Kerstin

    2017-04-01

    See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article.Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the 'law of effect'. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12-15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral electroencephalographic

  11. Does suprascapular nerve block reduce shoulder pain following stroke: a double-blind randomised controlled trial with masked outcome assessment

    Directory of Open Access Journals (Sweden)

    Crotty Maria

    2010-09-01

    Full Text Available Abstract Background Shoulder pain is a common complication of a stroke which can impede participation in rehabilitation programs and has been associated with poorer outcomes. The evidence base for current medical and therapeutic management options of hemiplegic shoulder pain is limited. This study will evaluate the use of suprascapular nerve block injection as part of an interdisciplinary approach to the treatment of shoulder pain following stroke. The technique has previously been proven safe and effective in the treatment of shoulder pain associated with rheumatoid arthritis and degenerative shoulder conditions but its usefulness in a stroke population is unclear. Methods/Design A double blind randomised placebo controlled trial will assess the effect of a suprascapular nerve block compared with placebo in a population of 66 stroke patients. The trial will measure effect of injection on the primary outcome of pain, and secondary outcomes of function and quality of life. Measurements will take place at baseline, and 1, 4 and 12 weeks post intervention. Both groups will continue to receive routine physiotherapy and standard ward care. Discussion The results of this study could reduce pain symptoms in persons with mechanical shoulder pain post stroke and provide improvement in upper limb function. Trial Registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR - ACTRN12609000621213.

  12. Sucralfate or placebo following argon plasma coagulation for chronic radiation proctitis: a randomized double blind trial.

    Science.gov (United States)

    Chruscielewska-Kiliszek, M R; Regula, J; Polkowski, M; Rupinski, M; Kraszewska, E; Pachlewski, J; Czaczkowska-Kurek, E; Butruk, E

    2013-01-01

    Chronic radiation proctitis is a long-term complication of radiation therapy for pelvic malignancy. The aim of this study was to compare the efficacy and safety of two treatment regimens, sucralfate or placebo, following argon plasma coagulation (APC) for chronic haemorrhagic radiation proctitis. A single-centre, randomized, placebo-controlled, double-blind study was performed on patients with haemorrhagic chronic radiation proctitis after irradiation for prostate, uterine, cervical, rectal or vaginal cancer. All patients received APC, and were then randomized to oral sucralfate (6 g twice a day) or placebo treatment for 4 weeks. APC was repeated every 8 weeks if necessary after the first session. Patients were graded clinically and endoscopically according to the Chutkan and Gilinski scales before and at 8 and 16 weeks after initial APC treatment (1.5-2 l/min, 25-40 W) and after 52 weeks (clinical only). Of 122 patients, 117 completed the entire protocol, with 57/60 in the sucralfate group and 60/62 in the placebo group. At baseline there were no significant differences between the sucralfate and placebo groups. At 1 year, a significant improvement in the clinical scale in both groups occurred compared with baseline. After 16 weeks, the median overall clinical severity scores fell from 4 to 2 points and the median bleeding score from 2 to 0 in both groups. APC is safe and effective for the management of chronic radiation proctitis. Additional sucralfate treatment did not influence the clinical or endoscopic outcome. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

  13. MRI findings in men on active surveillance for prostate cancer. Does dutasteride make MRI visible lesions less conspicuous? Results from a placebo-controlled, randomised clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Giganti, Francesco [University College London Hospital NHS Foundation Trust, Department of Radiology, London (United Kingdom); University College London, Division of Surgery and Interventional Science, London (United Kingdom); Moore, Caroline M.; Robertson, Nicola L.; Emberton, Mark [University College London, Division of Surgery and Interventional Science, London (United Kingdom); University College London Hospital NHS Foundation Trust, Department of Urology, London (United Kingdom); McCartan, Neil [University College London, Division of Surgery and Interventional Science, London (United Kingdom); Jameson, Charles [University College London Hospital NHS Foundation Trust, Department of Pathology, London (United Kingdom); Bott, Simon R.J. [Frimley Park Hospital, Department of Urology, Surrey (United Kingdom); Winkler, Mathias [Imperial College NHS Trust, Department of Urology, Charing Cross Hospital, London (United Kingdom); Gambarota, Giulio [INSERM, Rennes (France); Universite de Rennes 1, Rennes (France); Whitcher, Brandon [Klarismo, London (United Kingdom); Imperial College London, Department of Mathematics, London (United Kingdom); Castro, Ramiro [GlaxoSmithKline, Research and Development, Philadelphia, PA (United States); Allen, Clare; Kirkham, Alex [University College London Hospital NHS Foundation Trust, Department of Radiology, London (United Kingdom)

    2017-11-15

    To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo. We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed blind to treatment allocation and clinical information. Mean ADC of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between groups over 6 months. Conspicuity was defined as the PZ divided by tumour ADC, and its change over 6 months was assessed. A decrease in mean conspicuity in the dutasteride group (but not the controls) was seen over 6 months (1.54 vs 1.38; p = 0.025). Absolute changes in ADC and conspicuity were significantly different between placebo and dutasteride groups at 6 months: (-0.03 vs 0.08, p = 0.033) and (0.11 vs -0.16, p = 0.012), as were percentage changes in the same parameters: (-2.27% vs 8.56% p = 0.048) and (9.25% vs -9.89% p = 0.013). Dutasteride was associated with increased tumour ADC and reduced conspicuity. A lower threshold for triggering biopsy might be considered in men on dutasteride undergoing mpMRI for prostate cancer. (orig.)

  14. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib: an international, multicentre, prospective, randomised, placebo-controlled phase 3 trial (GRID)

    Science.gov (United States)

    Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo

    2013-01-01

    Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; pregorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib-related adverse events were hypertension (31/132, 23·5%), hand–foot skin reaction (26

  15. Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study.

    Science.gov (United States)

    Udani, Jay K

    2013-01-01

    To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18-61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine).

  16. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.

    Science.gov (United States)

    Chollet, François; Tardy, Jean; Albucher, Jean-François; Thalamas, Claire; Berard, Emilie; Lamy, Catherine; Bejot, Yannick; Deltour, Sandrine; Jaillard, Assia; Niclot, Philippe; Guillon, Benoit; Moulin, Thierry; Marque, Philippe; Pariente, Jérémie; Arnaud, Catherine; Loubinoux, Isabelle

    2011-02-01

    Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial

  17. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial.

    Science.gov (United States)

    Zenico, T; Cicero, A F G; Valmorri, L; Mercuriali, M; Bercovich, E

    2009-04-01

    Lepidium meyenii (Maca) is a cultivated root belonging to the brassica family used in the Andean region for its supposed aphrodisiac properties. We carried out a double-blind clinical trial on 50 Caucasian men affected by mild erectile dysfunction (ED), randomised to treatment with Maca dry extract, 2400 mg, or placebo. The treatment effect on ED and subjective well-being was tested administrating before and after 12 weeks the International Index of Erectile Function (IIEF-5) and the Satisfaction Profile (SAT-P). After 12 weeks of treatment, both Maca- and placebo-treated patients experienced a significant increase in IIEF-5 score (P Maca experienced a more significant increase than those taking placebo (1.6 +/- 1.1 versus 0.5 +/- 0.6, P Maca- and placebo-treated subjects experienced a significant improvement in psychological performance-related SAT-P score, but the Maca group higher than that of placebo group (+9 +/- 6 versus +6 +/- 5, P Maca-treated patients experienced a significant improvement in physical and social performance-related SAT-P score compared with the baseline (+7 +/- 6 and +7 +/- 6, both P Maca supplementation on subjective perception of general and sexual well-being in adult patients with mild ED.

  18. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  19. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial.

    Science.gov (United States)

    Mobeen, N; Durocher, J; Zuberi, Nf; Jahan, N; Blum, J; Wasim, S; Walraven, G; Hatcher, J

    2011-02-01

    to determine if misoprostol is safe and efficacious in preventing postpartum haemorrhage (PPH) when administered by trained traditional birth attendants (TBA) at home deliveries. a randomised, double-blind, placebo-controlled trial. Chitral, Khyber Pakhtunkhwa Province, Pakistan. a total of 1119 women giving birth at home. from June 2006 to June 2008, consenting women were randomised to receive 600 microg oral misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether misoprostol reduced the incidence of PPH (≥ 500 ml). the primary outcomes were measured blood loss ≥ 500 ml after delivery and drop in haemoglobin >2 g/dl from before to after delivery. oral misoprostol was associated with a significant reduction in the rate of PPH (≥ 500 ml) (16.5 versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable differences between study groups for drop in haemoglobin >2 g/dl (relative risk 0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common with misoprostol. There were no maternal deaths among participants. postpartum administration of 600 microg oral misoprostol by trained TBAs at home deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost, misoprostol could reduce the burden of PPH in community settings where universal oxytocin prophylaxis is not feasible. Continual training and skill-building for TBAs, along with monitoring and evaluation of programme effectiveness, should accompany any widespread introduction of this drug.

  20. An international randomised placebo-controlled trial of a four-component combination pill ("polypill" in people with raised cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Anthony Rodgers

    Full Text Available There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills' to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP, LDL-cholesterol and tolerability (proportion discontinued randomised therapy at 12 weeks follow-up.At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1 mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9 mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2. There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001, which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

  1. Prevalence of lactose intolerance in Chile: a double-blind placebo study.

    Science.gov (United States)

    Latorre, Gonzalo; Besa, Pablo; Parodi, Carmen G; Ferrer, Verónica; Azocar, Lorena; Quirola, Marife; Villarroel, Luis; Miquel, Juan F; Agosin, Eduardo; Chianale, José

    2014-01-01

    Lactase non-persistence (LNP), or primary hypolactasia, is a genetic condition that mediates lactose malabsorption and can cause lactose intolerance. Here we report the prevalence of lactose intolerance in a double-blind placebo study. The LCT C>T-13910 variant was genotyped by RT-PCR in 121 volunteers and lactose malabsorption was assessed using the hydrogen breath test (HBT) after consuming 25 g of lactose. Lactose intolerance was assessed by scoring symptoms (SS) using a standardized questionnaire following challenge with a lactose solution or saccharose placebo. The LNP genotype was observed in 57% of the volunteers, among whom 87% were HBT⁺. In the HBT⁺ group the median SS was 9 and in the HBT⁻ group the median SS was 3 (p lactose intolerance was defined as the presence of an SS ≥ 6 points after subtracting the placebo effect and 34% of the study population met this definition. The LNP genotype was present in more than half of subjects evaluated and the observed prevalence of lactose intolerance was 34%. © 2014 S. Karger AG, Basel.

  2. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

    Science.gov (United States)

    Dannon, P N; Sasson, Y; Hirschmann, S; Iancu, I; Grunhaus, L J; Zohar, J

    2000-05-01

    To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

  3. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

    Science.gov (United States)

    2014-01-01

    Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

  4. Esomeprazole treatment of frequent heartburn: two randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Peura, David A; Traxler, Barry; Kocun, Christopher; Lind, Tore

    2014-07-01

    To determine the efficacy of a 14-day regimen of esomeprazole 20 mg for the treatment of frequent heartburn in subjects who are likely to self-treat with over-the-counter medications without consulting a health care provider. Adults with frequent heartburn ≥ 2 days per week in the past 4 weeks were randomly assigned to 14-day double-blind treatment with esomeprazole 20 mg once daily or placebo in 2 identical multicenter studies (ClinicalTrials.gov identifiers: NCT01370525, NCT01370538). The primary efficacy outcome was percentage of heartburn-free 24-hour days across 14 days. Secondary efficacy outcomes included heartburn resolution, defined as heartburn ≤ 2 days over 14 days, and percentages of subjects reporting ≤ 1 day with heartburn in the first and final weeks of treatment. Subjects recorded data in daily self-assessment diaries. The percentage of heartburn-free 24-hour days over 14 days was significantly higher (P heartburn resolution over 14 days and in the first and final weeks compared with placebo. Within the first 4 days, the proportion of subjects with heartburn-free days was significantly greater with esomeprazole 20 mg versus placebo. Treatment was generally well tolerated, with a safety pattern consistent with the known profile for esomeprazole. A 14-day regimen of esomeprazole 20 mg once daily was effective for treating frequent heartburn in subjects who are likely to self-treat with over-the-counter medications.

  5. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The efficacy of azithromycin in pityriasis rosea: A randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Deepika Pandhi

    2014-01-01

    Full Text Available Background: Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment. Aim: A randomized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea. Methods: Seventy patients of pityriasis rosea were given either azithromycin (n = 35 or placebo (n = 35 and were followed-up at 2, 4 and 6 weeks. Pruritus was assessed in both groups using the visual analogue scale (VAS . Change in the pityriasis rosea severity score (PRSS and in the VAS were recorded as outcome measures and were compared statistically. Results: The decrease in PRSS from baseline through 2, 4 and 6 weeks within both treatment (P < 0.001 and placebo (P < 0.001 arms was found to be statistically significant; however, this change was not significantly different in the two groups (P = 0.179. Similarly, the decrease in VAS was found to be statistically significant within both groups (P < 0.001; however, the change was comparable between the two groups (P < 0.937. Analysis by Fisher′s exact test did not find a significant difference between the two groups for PRSS and VAS. Conclusion: Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice.

  7. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study.

    Science.gov (United States)

    Akhtari, Elham; Raisi, Firoozeh; Keshavarz, Mansoor; Hosseini, Hamed; Sohrabvand, Farnaz; Bioos, Soodabeh; Kamalinejad, Mohammad; Ghobadi, Ali

    2014-04-28

    Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

  8. Randomised clinical trial

    DEFF Research Database (Denmark)

    Reimer, C; Lødrup, A; Smith, G

    2016-01-01

    of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. MethodsThis was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...

  9. Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Gøtzsche, Peter C; Hróbjartsson, Asbjørn

    2009-01-01

    OBJECTIVES: To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture. DESIGN: Systematic review and meta-analysis of three armed randomised clinical trials. DATA SOURCES......: Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis Standardised mean differences from each trial were used to estimate the effect of acupuncture and placebo acupuncture. The different types of placebo acupuncture were ranked from 1 to 5 according...... to assessment of the possibility of a physiological effect, and this ranking was meta-regressed with the effect of acupuncture. DATA SYNTHESIS: Thirteen trials (3025 patients) involving a variety of pain conditions were eligible. The allocation of patients was adequately concealed in eight trials...

  10. Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients.

    Science.gov (United States)

    W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

    2012-01-01

    Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds.

  11. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

    NARCIS (Netherlands)

    Panés, Julian; Sandborn, William J.; Schreiber, Stefan; Sands, Bruce E.; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D. R.; Colombel, Jean-Frederic; Feagan, Brian G.; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

    2017-01-01

    Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind,

  12. Lactobacillus reuteri influences regrowth of mutans streptococci after full-mouth disinfection: a double-blind, randomised controlled trial.

    Science.gov (United States)

    Romani Vestman, N; Hasslöf, P; Keller, M K; Granström, E; Roos, S; Twetman, S; Stecksén-Blicks, C

    2013-01-01

    This study assessed whether the persistence of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 in saliva could delay the regrowth of mutans streptococci (MS) after a full-mouth disinfection with chlorhexidine (CHX). A randomised, double-blind, placebo-controlled study with a 6-week intervention period and 3- and 6-month follow-up was performed. 62 healthy subjects with moderate to high counts of MS were randomly assigned to a test group (n = 32) or a placebo group (n = 30). Before onset of the intervention, subjects received two sessions of professional cleaning, flossing, and application of CHX varnish and rinsed their mouth with a CHX solution between the sessions (2 days). Thereafter, the test group used probiotic lozenges (2/day) containing L. reuteri (DSM 17938 and ATCC PTA 5289; 1 × 10(8) CFU of each strain), and the placebo group used identical lozenges lacking the lactobacilli. Saliva samples were collected and cultured onto selective media, and isolates of L. reuteri as well as DNA directly extracted from saliva were tested by polymerase chain reaction (PCR) with specific primers. Presence of salivary MS was analysed with a chair-side test. L. reuteri was frequently detected by culture during the intervention period but in only 3 test group subjects at follow-ups. Regrowth of MS statistically significantly differed depending on the presence or absence of L. reuteri DSM 17938 detected by PCR. We conclude that cultivable L. reuteri strains may only sporadically be confirmed after termination of the intervention, but subjects with PCR-detected L. reuteri demonstrated slower regrowth of MS. Copyright © 2013 S. Karger AG, Basel.

  13. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study

    OpenAIRE

    Krymchantowski,Abouch V.; Barbosa,Jackeline S.; Cheim,Celia; Alves,Luiz A.

    2001-01-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, wer...

  14. Efficacy of polyglucosamine for weight loss?confirmed in a randomized double-blind, placebo-controlled clinical investigation

    OpenAIRE

    Pokhis, Karina; Bitterlich, Norman; Cornelli, Umberto; Cassano, Giuseppina

    2015-01-01

    Background The purpose of this clinical study was to ascertain whether low molecular weight chitosan polyglucosamine is able to produce significantly better weight loss than placebo. Method 115 participants were included in the study. We used a two-center randomized, double blind, placebo-controlled design. The participants followed a standard treatment (ST), which included the combination of a low-calorie diet achieved through creating a daily calorie deficit (500 cal) and an increased daily...

  15. Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Phillips, Katharine A; Keshaviah, Aparna; Dougherty, Darin D; Stout, Robert L; Menard, William; Wilhelm, Sabine

    2016-09-01

    Body dysmorphic disorder is common, distressing, and often severely impairing. Serotonin reuptake inhibitors appear efficacious, but the few existing pharmacotherapy studies were short term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted to the authors' knowledge. The authors report results from the first relapse prevention study in body dysmorphic disorder. Adults (N=100) with DSM-IV body dysmorphic disorder received open-label escitalopram for 14 weeks (phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for 6 months (phase 2). Reliable and valid outcome measures were utilized. In phase 1, 67.0% of treated subjects and 81.1% of subjects who completed phase 1 responded to escitalopram. Body dysmorphic disorder severity (in both the intent-to-treat and the completer groups) and insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of phase 1. In phase 2, time to relapse was significantly longer with escitalopram than with placebo treatment (hazard ratio=2.72, 95% CI=1.01-8.57). Phase 2 relapse proportions were 18% for escitalopram and 40% for placebo. Among escitalopram-treated subjects, body dysmorphic disorder severity significantly decreased over time during the continuation phase, with 35.7% of subjects showing further improvement. There were no significant group differences in body dysmorphic disorder severity or insight, depressive symptoms, psychosocial functioning, or quality of life. Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed than did placebo-treated subjects. Body dysmorphic disorder severity significantly improved during 6 additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects experienced further improvement.

  16. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

    2009-05-01

    Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

  17. Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

    2016-02-01

    Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

  18. Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

    2017-12-01

    To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P gout flares (29.3% versus 41.4%; P gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

  19. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study.

    Science.gov (United States)

    Santos, C A; Reis, L O; Destro-Saade, R; Luiza-Reis, A; Fregonesi, A

    2014-05-01

    To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels. Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way. The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914). At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total

  20. A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Skovbjerg, Sine; Arendt-Nielsen, Lars

    2017-01-01

    was the Life Impact Scale (LIS) of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Secondary outcomes were the Symptom Severity Scale (SSS) and the Chemical Intolerance Scale of QEESI. RESULTS: A total of 39 participants were randomised to PEMF or placebo treatment. No significant...... difference was observed on QEESI LIS between groups with a mean change score of -5.9 in the PEMF group compared with -1.5 in the placebo group (p=0.35, effect size=-0.31). However, a significant decrease was detected on QEESI SSS within and between groups with a mean change score of -11.3 in the PEMF group...

  1. Aspartame Sensitivity? A Double Blind Randomised Crossover Study

    OpenAIRE

    Sathyapalan, Thozhukat; Thatcher, Natalie J.; Hammersley, Richard; Rigby, Alan S.; Pechlivanis, Alexandros; Gooderham, Nigel J.; Holmes, Elaine; le Roux, Carel W.; Atkin, Stephen L.; Courts, Fraser

    2015-01-01

    Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight indivi...

  2. Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Andrew Scholey

    2017-02-01

    Full Text Available Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6, in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171 were randomized (1:1 to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

  3. Field assessment of a novel household-based water filtration device: a randomised, placebo-controlled trial in the Democratic Republic of Congo.

    Science.gov (United States)

    Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

    2010-09-10

    Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61-1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (pwater the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Current Controlled Trials ISRCTN03844341.

  4. A randomised placebo-controlled trial of a traditional Chinese herbal formula in the treatment of primary dysmenorrhoea.

    Directory of Open Access Journals (Sweden)

    Lan Lan Liang Yeh

    Full Text Available BACKGROUND: Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. METHODOLOGY/PRINCIPAL FINDINGS: A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow

  5. Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.

    Science.gov (United States)

    Mathie, Robert T; Clausen, Jürgen

    2015-01-01

    Meta-analysis of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. For all medical conditions and species collectively, we tested the hypothesis that the outcome of homeopathic intervention (treatment and/or prophylaxis, individualised and/or non-individualised) is distinguishable from corresponding intervention using placebos. All facets of the review, including literature search strategy, study eligibility, data extraction and assessment of risk of bias, were described in an earlier paper. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specific domains of assessment. Effect size was reported as odds ratio (OR). A trial was judged free of vested interest if it was not funded by a homeopathic pharmacy. Meta-analysis was conducted using the random-effects model, with hypothesis-driven sensitivity analysis based on risk of bias. Nine of 15 trials with extractable data displayed high risk of bias; low or unclear risk of bias was attributed to each of the remaining six trials, only two of which comprised reliable evidence without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95% confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02). Meta-analysis provides some very limited evidence that clinical intervention in animals using homeopathic medicines is distinguishable from corresponding intervention using placebos. The low number and quality of the trials hinders a more decisive conclusion. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  6. A safety analysis of edaravone (MCI-186) during the first six cycles (24 weeks) of amyotrophic lateral sclerosis (ALS) therapy from the double-blind period in three randomized, placebo-controlled studies.

    Science.gov (United States)

    Kalin, Alexander; Medina-Paraiso, Elvia; Ishizaki, Kaoru; Kim, Alex; Zhang, Yannong; Saita, Takanori; Wasaki, Masahiko

    2017-10-01

    There continues to be a need for new therapies to treat ALS. Provide an overview of safety for edaravone in ALS patients during the first six cycles of treatment. Analysis was based on three randomised, placebo-controlled clinical trials. Endpoints included treatment-emergent adverse events (TEAEs), including AEs leading to discontinuation, serious adverse events (SAEs), and deaths. The analysis included a total of 368 patients (184 in the edaravone group and placebo group, respectively). Of those, 94.6% of the edaravone group and 90.2% of placebo group completed six cycles of therapy. Baseline characteristics were comparable between the two groups. TEAE incidence in the edaravone group and placebo group was 87.5% and 87.0%, respectively. TEAEs ocurring at ≥2% incidence in the edaravone group compared to placebo were contusion (14.7% vs. 8.7%), gait disturbance (12.5% vs. 9.2%), headache (8.2% vs. 5.4%), eczema (6.5% vs. 2.2%), dermatitis contact (6.0% vs. 3.3%), respiratory disorder (4.3% vs. 1.1%), and glucose urine present (3.8% vs. 1.6%). There was no imbalance in TEAEs leading to discontinuation (2.2% [edaravone], and 5.4% [placebo]). SAE incidence was 17.4% in the edaravone group and 22.3% in placebo group. Treatment-emergent deaths occurred in 2.2% in the edaravone group and 1.1% in placebo group, all respiratory in nature and attributed to worsening ALS. Data collected from three double-blind assessments found that while some TEAEs were more common in the edaravone group compared to placebo, the overall incidences of SAEs, deaths, and discontinuations due to AEs were similar or less for edaravone compared to placebo.

  7. Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

    Science.gov (United States)

    Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

    2017-09-08

    In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial.

    Science.gov (United States)

    Malay, D Scot; Pressman, Martin M; Assili, Amir; Kline, Jason T; York, Shane; Buren, Ben; Heyman, Eugene R; Borowsky, Pam; LeMay, Carley

    2006-01-01

    Extracorporeal shockwave therapy (ESWT) has demonstrated efficacy in the treatment of recalcitrant proximal plantar fasciitis. The objective of this investigation was to compare the outcomes of participants treated with a new ESWT device with those treated with placebo. A total of 172 volunteer participants were randomized in a 2:1 active-to-placebo ratio in this prospective, double-blind, multicenter trial conducted between October 2003 and December 2004. ESWT (n=115) or placebo control (n=57) was administered on a single occasion without local or systemic anesthesia or sedation, after which follow-up was undertaken. The primary outcomes were the blind assessor's objective, and the participant's subjective assessments of heel pain during the first 3 months of follow-up. Participants were also followed up to 1 year to identify any adverse outcomes that may have been related to the shockwave device. On the visual analog scale, the blind assessor's objective assessment of heel pain displayed a mean reduction of 2.51 in the shockwave group and 1.57 in the placebo group; this difference was statistically significant (P=.045). On the visual analog scale, the participant's self-assessment of heel pain displayed a mean reduction of 3.39 in the shockwave group and 1.78 in the placebo group; this difference was statistically significant (P<.001). No serious adverse events were observed at any time. It was concluded that ESWT was both efficacious and safe for participants with chronic proximal plantar fasciitis that had been unresponsive to exhaustive conservative treatment.

  9. Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial.

    Science.gov (United States)

    Moshe, Keren; Karni, Avi; Tirosh, Emanuel

    2012-09-01

    To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12 years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.

  10. Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

    Science.gov (United States)

    Momsen, A H; Jensen, M B; Norager, C B; Madsen, M R; Vestersgaard-Andersen, T; Lindholt, J S

    2010-10-01

    Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication. This randomized double-blind placebo-controlled crossover study included 88 patients recruited by surgeons from outpatient clinics. The participants abstained from caffeine for 48 h before each test and then received either a placebo or oral caffeine (6 mg/kg). After 75 min, pain-free and maximal walking distance on a treadmill, perceived pain, reaction times, postural stability, maximal isometric knee extension strength, submaximal knee extension endurance and cognitive function were measured. The analysis was by intention to treat. Caffeine increased the pain-free walking distance by 20.0 (95 per cent confidence interval 3.7 to 38.8) per cent (P = 0.014), maximal walking distance by 26.6 (12.1 to 43.0) per cent (P postural stability was reduced significantly, by 22.1 (11.7 to 33.4) per cent with eyes open (P < 0.001) and by 21.8 (7.6 to 37.8) per cent with eyes closed (P = 0.002). Neither reaction time nor cognition was affected. In patients with moderate intermittent claudication, caffeine increased walking distance, maximal strength and endurance, but affected balance adversely.

  11. Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

    Science.gov (United States)

    Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

    2015-03-01

    In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

    Science.gov (United States)

    de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

    2001-01-01

    We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

  13. Randomized, double-blind, placebo-controlled trial using lidocaine patch 5% in traumatic rib fractures.

    Science.gov (United States)

    Ingalls, Nichole K; Horton, Zachary A; Bettendorf, Matthew; Frye, Ira; Rodriguez, Carlos

    2010-02-01

    The lidocaine patch 5% was developed to treat postherpetic neuralgia. Anecdotal experience at our institution suggests the lidocaine patch 5% decreases narcotic usage in patients with traumatic rib fractures. This trial was developed to define the patch's efficacy. Patients with rib fractures admitted to the trauma service at our Level I trauma center were enrolled and randomized in a 1 to 1 double-blind manner to receive a lidocaine patch 5% or placebo patch. Fifty-eight patients who met the inclusion criteria were enrolled from January 2007 to August 2008. Demographic and clinical information were recorded. The primary outcomes variable was total narcotic use, analyzed using the 1-tailed Mann-Whitney test. The secondary outcomes variables included non-narcotic pain medication, average pain score, pulmonary complications, and length of stay. Significance was defined based on a 1-sided test for the primary outcome and 2-sided tests for other comparisons, at p rib fractures, gender, trauma mechanism, preinjury lung disease, smoking history, percent of current smokers, and need for placement of chest tube between the lidocaine patch 5% and placebo groups. There was no difference between the lidocaine patch 5% and placebo groups, respectively, with regard to total IV narcotic usage: median, 0.23 units versus 0.26 units; total oral narcotics: median, 4 units versus 7 units; pain score: 5.6 +/- 0.4 versus 6.0 +/- 0.3 (mean +/- SEM); length of stay: 7.8 +/- 1.1 versus 6.2 +/- 0.7; or percentage of patients with pulmonary complications: 72.7% versus 72.0%. The lidocaine patch 5% does not significantly improve pain control in polytrauma patients with traumatic rib fractures.

  14. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

  15. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

    Science.gov (United States)

    Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

    2011-01-01

    Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

  16. Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dubé syndrome: a double-blind placebo-controlled randomized split-face trial.

    Directory of Open Access Journals (Sweden)

    Lieke M C Gijezen

    Full Text Available Birt-Hogg-Dubé syndrome (BHD is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR. Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD.We performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects.No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients as well as the placebo treated facial sides (both 74%. No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion. No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients than after placebo (58% of patients; p = 0.625. A burning sensation, erythema, itching and dryness were most frequently reported.This study provides no evidence that treatment of fibrofolliculomas with topical

  17. A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

    Science.gov (United States)

    Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

    2017-07-28

    Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

  18. Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial.

    LENUS (Irish Health Repository)

    O'Sullivan, A

    2012-02-01

    OBJECTIVE: To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck (NNS) as a method for reducing pain associated with retinopathy of prematurity (ROP) screening. DESIGN: Randomised placebo controlled study. SETTING: Tertiary level neonatal intensive care unit. SAMPLE: 40 infants undergoing primary eye examination for ROP screening. INTERVENTION: The control group were swaddled, and received 0.2 ml of sterile water given by mouth using a syringe and a soother. The intervention group were swaddled, and received 0.2 ml of sucrose 24% given by mouth using a syringe and a soother. RESULTS: 40 infants were included in the study. There was no difference in mean gestational age at birth, mean birth weight or corrected gestational age at first examination between both groups. The sucrose group had a significantly lower median Neonatal Pain, Agitation and Sedation Scale (N-PASS) score during ROP screening, initially following insertion of the speculum (6.5 vs 5, p=0.02) and subsequently during scleral indentation (9.5 vs 7.5, p=0.03). Fewer infants experienced episodes of desaturations or bradycardia in the intervention group (1 vs 4, p=0.18). CONCLUSION: ROP screening is a necessary but recognised painful procedure. Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses. However, pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge.

  19. High-volume infiltration analgesia in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Andersen, L.O.; Husted, H.; Otte, K.S.

    2008-01-01

    with a detailed description of the infiltration technique. METHODS: In a randomized, double-blind, placebo-controlled trial in 12 patients undergoing bilateral knee arthroplasty, saline or high-volume (170 ml) ropivacaine (0.2%) with epinephrine was infiltrated around each knee, with repeated doses administered...

  20. Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial

    NARCIS (Netherlands)

    van der Bom, Teun; Winter, Michiel M.; Bouma, Berto J.; Groenink, Maarten; Vliegen, Hubert W.; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

    2013-01-01

    The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a

  1. Cognitive, health and psychosocial effects of melatonin and light therapy in childhood insomnia. Double-blind placebo-controlled study

    NARCIS (Netherlands)

    Smits, M.; van Maanen, A.; Meijer, A.M.; van der Heijden, K.; Oort, F.

    2017-01-01

    Introduction: To examine effects of melatonin and light therapy on cognitive, health and psychosocial outcomes in children with chronic sleep onset insomnia; and to disentangle direct effects from indirect effects through sleep improvement. Methods: A randomized, double-blind placebo-controlled

  2. Masking foods for food challenge: practical aspects of masking foods for a double-blind, placebo-controlled food challenge

    NARCIS (Netherlands)

    Huijbers, G. B.; Colen, A. A.; Jansen, J. J.; Kardinaal, A. F.; Vlieg-Boerstra, B. J.; Martens, B. P.

    1994-01-01

    In diagnosing a food allergy or food intolerance, a double-blind, placebo-controlled food challenge (DBPCFC) with the suspected food or food substance is the only method available for objective confirmation of an assumed relationship between a suspected agent and a complaint. When the use of

  3. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results

    DEFF Research Database (Denmark)

    Pastorello, Elide A; Vieths, Stefan; Pravettoni, Valerio

    2002-01-01

    The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients...

  4. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

    NARCIS (Netherlands)

    Westenberg, HGM; Stein, DJ; Yang, HC; Li, D; Barbato, LM

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to

  5. Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Thamsborg, G; Florescu, A; Oturai, P

    2005-01-01

    OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial. DESIGN: The trial consisted of 2h daily treatment 5 days per...

  6. Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    de Waal, Yvonne C. M.; Raghoebar, Gerry M.; Huddleston Slater, James J. R.; Meijer, Henny J. A.; Winkel, Edwin G.; van Winkelhoff, Arie Jan

    Aim The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. Material & Methods Thirty patients (79 implants) with

  7. Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    de Waal, Yvonne C.M.; Raghoebar, Gerry M; Huddleston Slater, James J R; Meijer, Hendrikus; Winkel, Edwin G; van Winkelhoff, Arie Jan

    AIM: The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. MATERIAL & METHODS: Thirty patients (79 implants) with

  8. Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II

    NARCIS (Netherlands)

    Versyck, B.; Geffen, G.J. van; Houwe, P. Van

    2017-01-01

    STUDY OBJECTIVE: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. DESIGN: A prospective randomized double blind placebo-controlled study. SETTING:

  9. A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

    OpenAIRE

    Kambiz Eftekhari; Zahra Vahedi; Mojtaba Kamali Aghdam; Diana Noemi Diaz

    2015-01-01

    Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to ...

  10. Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, BJ; Bijleveld, CMA; van der Heide, S; Beusekamp, BJ; Wolt-Plompen, SAA; Kukler, J; Brinkman, J; Duiverman, EJ; Dubois, AEJ

    Background: The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. Objective: The purpose of this study was to develop and validate

  11. A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

    Science.gov (United States)

    Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

    2012-01-01

    Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

  12. Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Jörg Täubel

    Full Text Available Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK, pharmacodynamics (PD, safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP, reaction time (RT, spatial working memory (SWM and visual analogue scales (VAS.Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs or withdrawals due to treatment-emergent adverse events (TEAEs in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.

  13. Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol

    Science.gov (United States)

    Schnadower, David; Tarr, Phillip I; Charles, Casper T; Gorelick, Marc H; Dean, Michael J; O’Connell, Karen J; Mahajan, Prashant; Chun, Thomas H; Bhatt, Seema R; Roskind, Cindy G; Powell, Elizabeth C; Rogers, Alexander J; Vance, Cheryl; Sapien, Robert E; Gao, Feng; Freedman, Stephen B

    2017-01-01

    Introduction Acute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE. Methods and analysis The study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (1010colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified. Ethics and dissemination Institutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures. Trial registration number

  14. Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

    Science.gov (United States)

    Robb, Adelaide; Bose, Anjana

    2013-01-01

    Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

  15. Effect of nitrous oxide on pain due to rocuronium injection: A randomised, double-blind, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Sonal Sharma

    2010-01-01

    Full Text Available A prospective, randomised, double-blind, placebo-controlled study was carried out to determine the effect of nitrous oxide (N 2 O on the frequency and severity of pain and withdrawal reactions after injection of rocuronium. Eighty ASA physical status I and II patients undergoing general anaesthesia for elective surgery were enrolled. The patients were randomised to receive 100% oxygen (O 2 , or 50% N 2 O in O 2 for 3 minutes followed by a subparalysing dose of rocuronium 0.06 mg/kg. After induction of anaesthesia with thiopentone 5 mg/kg, an intubating dose of rocuronium 0.6 mg/kg was given. The patients were observed after injection of rocuronium 0.06 mg/kg, and asked to rate pain in the arm on a 4-point (0-3 verbal rating scale (none, mild, moderate or severe. After the intubating dose of rocuronium, withdrawal reactions were recorded. Thirty-six patients (90% in the group N 2 O and 15 patients (37.5% in the group O 2 reported no pain (P < 0.001. The pain was mild in 1 (2.5% and 9 (22.5% patients in N 2 O and O 2 groups, respectively (P = 0.006. Moderate pain occurred in 2 (5% patients in group N 2 O and 15 (37.5% patients in group O 2 (P = 0.001. Severe pain was reported by one patient in each group (P = 0.47. Withdrawal response after an intubating dose of rocuronium was observed in 6 (15% and 18 (45% patients in the N 2 O and O 2 groups, respectively (P < 0.05. Inhalation of 50% N 2 O in O 2 reduces the incidence and severity of pain and the withdrawal reactions associated with rocuronium injection.

  16. The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

    Science.gov (United States)

    Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

    2017-07-01

    Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

  17. Remifentanil versus placebo for analgesia during external cephalic version: a randomised clinical trial.

    Science.gov (United States)

    Muñoz, H; Guerra, S; Perez-Vaquero, P; Valero Martinez, C; Aizpuru, F; Lopez-Picado, A

    2014-02-01

    Breech presentation occurs in up to 3% of pregnancies at term and may be an indication for caesarean delivery. External cephalic version can be effective in repositioning the fetus in a cephalic presentation, but may be painful for the mother. Our aim was to assess the efficacy of remifentanil versus placebo for pain relief during external cephalic version. A randomized, double-blind, controlled trial that included women at 36-41 weeks of gestation with non-cephalic presentations was performed. Women were randomized to receive either a remifentanil infusion at 0.1 μg/kg/min and demand boluses of 0.1 μg/kg, or saline placebo. The primary outcome was the numerical rating pain score (0-10) after external cephalic version. Sixty women were recruited, 29 in the control group and 31 in the remifentanil group. There were significant differences in pain scores at the end of the procedure (control 6.5 ± 2.4 vs. remifentanil 4.7 ± 2.5, P = 0.005) but not 10 min later (P = 0.054). The overall success rate for external cephalic version was 49% with no significant differences between groups (remifentanil group 54.8% vs. control group 41.3%, P = 0.358). In the remifentanil group, there was one case of nausea and vomiting, one of drowsiness and three cases of fetal bradycardia. In the control group, there were three cases of nausea and vomiting, one of dizziness and nine cases of fetal bradycardia. Intravenous remifentanil with bolus doses on demand during external cephalic version achieved a reduction in pain and increased maternal satisfaction. There were no additional adverse effects, and no difference in the success rate of external cephalic version or the incidence of fetal bradycardia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

    Science.gov (United States)

    Paulsen, Gøran; Cumming, Kristoffer T; Holden, Geir; Hallén, Jostein; Rønnestad, Bent Ronny; Sveen, Ole; Skaug, Arne; Paur, Ingvild; Bastani, Nasser E; Østgaard, Hege Nymo; Buer, Charlotte; Midttun, Magnus; Freuchen, Fredrik; Wiig, Havard; Ulseth, Elisabeth Tallaksen; Garthe, Ina; Blomhoff, Rune; Benestad, Haakon B; Raastad, Truls

    2014-04-15

    In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests

  19. Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial.

    Science.gov (United States)

    Boeke, A J; Dekker, J H; van Eijk, J T; Kostense, P J; Bezemer, P D

    1993-01-01

    OBJECTIVE--To compare the effect of lactic acid locally, metronidazole orally and placebo in women with bacterial vaginosis. DESIGN--Randomised clinical trial. SETTING--30 general practices in the Netherlands. PATIENTS--125 women consulting the general practitioner for symptomatic bacterial vaginosis. MAIN OUTCOME MEASURES--Duration of subjective symptoms, recurrence of symptoms, clinically diagnosed cure, adverse events. RESULTS--Survival analysis showed a significantly faster disappearance of symptoms in the metronidazole category compared with both lactic acid and placebo (p = 0.0005 metronidazole v placebo, p = 0.0002 metronidazole v lactic acid p = 0.6521 lactic acid v placebo [The stratified Mantel Cox test]). The median duration until absence of symptoms was 21 days for metronidazole and 80 days for placebo. Disappearance of symptoms did not occur in 50% of the lactic acid group in 90 days. Recurrence rates of symptoms were similar over the treatment categories (p = 0.13 metronidazole v placebo and p = 0.12 lactic acid v placebo). After 2 weeks cure rates (cure defined as less than three of four clinical criteria present) were 83%, 49% and 47% for metronidazole, lactic acid and placebo category respectively. At that time cure rates (cure defined as none of three clinical criteria present) were 10%, 0% and 3%. After four weeks and three months these figures were: 55%, 20%, 20% and 64%, 28%, 28%. No differences in adverse events were found between the three interventions. CONCLUSIONS--Lactic acid suppositories are ineffective, metronidazole capsules are effective on signs and symptoms in bacterial vaginosis. A considerable proportion of the patients recover without active medication. PMID:8244360

  20. Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.

    Science.gov (United States)

    Soler, Joaquim; Pascual, Juan Carlos; Campins, Josefa; Barrachina, Judith; Puigdemont, Dolors; Alvarez, Enrique; Pérez, Victor

    2005-06-01

    The aim of this study was to determine the efficacy and safety of dialectical behavior therapy plus olanzapine compared with dialectical behavior therapy plus placebo in patients with borderline personality disorder. Sixty patients with borderline personality disorder were included in a 12-week, double-blind, placebo-controlled study. All patients received dialectical behavior therapy and were randomly assigned to receive either olanzapine or placebo following a 1-month baseline period. Seventy percent of the patients completed the 4-month trial. Combined treatment showed an overall improvement in most symptoms studied in both groups. Olanzapine was associated with a statistically significant improvement over placebo in depression, anxiety, and impulsivity/aggressive behavior. The mean dose of olanzapine was 8.83 mg/day. A combined psychotherapeutic plus pharmacological approach appears to lower dropout rates and constitutes an effective treatment for borderline personality disorder.

  1. Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial.

    Science.gov (United States)

    Bruzzese, Eugenia; Raia, Valeria; Ruberto, Eliana; Scotto, Riccardo; Giannattasio, Antonietta; Bruzzese, Dario; Cavicchi, Maria Cristina; Francalanci, Michela; Colombo, Carla; Faelli, Nadia; Daccò, Valeria; Magazzù, Giuseppe; Costa, Stefano; Lucidi, Vincenzina; Majo, Fabio; Guarino, Alfredo

    2017-11-08

    Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). A multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6months of baseline assessment, enrolled children (2 to 16years of age) received Lactobacillus GG (6×10 9 CFU/day) or placebo for 12months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. Ninety-five patients were enrolled (51/95 female; median age of 103±50months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p=0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p=0.211). No significant difference was found for body mass index and FEV1. LGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  2. Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial.

    Science.gov (United States)

    Vickers, A J; van Haselen, R; Heger, M

    2001-04-01

    To pilot a method for determining whether homeopathically prepared mercury causes more symptoms (a "drug proving") in healthy volunteers than placebo. One hundred and eighteen (118) healthy volunteers ages 18 to 65 were recruited by local advertising. Subjects unfamiliar with homeopathy undertook a 1-week single-blind placebo run-in, a 1-week of double-blind, randomized treatment on either homeopathically prepared mercury 12C or placebo, and a third week of placebo run-out. Each day, symptoms were recorded on a checklist that included both true mercury symptoms and symptoms not expected to be caused by mercury (false symptoms). Additional symptoms were assessed by open reporting. Outcome was assessed by calculating a score for each day as the number of true symptoms minus the number of false symptoms. The mean score during placebo was then subtracted from the mean score for weeks two and three of the trial. Fourteen (14) subjects dropped out during placebo run-in. The remaining 104 completed the trial. Baseline comparability was good. Mean difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for placebo (p > 0.2). No significant differences between groups were found for the number of subjects meeting predefined criteria for a drug-proving reaction. This pilot study failed to find evidence that mercury 12C causes significantly more symptoms in healthy volunteers than placebo. Questionnaires with a limited number of gross symptoms do not seem to be an appropriate methodological technique in drug proving research. If drug-proving phenomena exist, they appear to be rare.

  3. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

    Science.gov (United States)

    Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

    2014-01-01

    Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

  4. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

    Science.gov (United States)

    Krymchantowski, A V; Barbosa, J S; Cheim, C; Alves, L A

    2001-03-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

  5. Effects of preoperative magnesium sulphate on post-cesarean pain, a placebo controlled double blind study.

    Directory of Open Access Journals (Sweden)

    Seyed Mohamad Mireskandari

    2015-03-01

    Full Text Available To study the role of preoperative intravenous magnesium sulphate in decreasing post-cesarean pain and opioid requirement during first 24hrs.In a double blind randomized clinical trial, prior to induction of general anesthesia, fifty elective cesarean candidates were randomly assigned to one of the two groups of placebo or magnesium sulfate. After surgery visual analogue scale (VAS and infused morphine by PCA during 24 hrs were recorded. The data were analyzed by mann-Whitney -test, analysis of variance, and student t- test.VAS was significantly lower among patients in the magnesium sulphate group at intervals of 1(st, 6(th & 12(th hours after cesarean section (C/S with the mean scales of (48.9 ± 19.6 VS 74.7 ± 18.4, (42.1 ± 0.9 VS 58.3 ± 16.5 and (25.2 ± 6.1VS 30 ± 8.1 respectively and p-value of <0.001, 0.002 and 0.05 respectively. However at 24 hrs there was no significant difference in VAS with mean VAS scales of 22.6 ± 4.5 VS 23.6 ± 4.9 and p-value of 0.49. The dose of infused Morphine during 24 hrs was significantly less in the magnesium sulphate group than the placebo group with the means of 4.36 ± 1.4 VS 7.02 ± 1.9 mg respectively (p < 0.001.Administration of bolus 50 mg/kg magnesium sulphate prior to induction of general anesthesia may significantly decreased the morphine requirement during immediate post operative period and can be recommended as one of the modalities of post-operative pain control in the pregnant patients.

  6. Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder.

    Science.gov (United States)

    Rezaei, Vala; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Sahraian, Ali; Tabrizi, Mina; Rezazadeh, Shams-Ali; Akhondzadeh, Shahin

    2010-10-01

    Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate+risperidone (Group A) or placebo+risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for 30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence.

    Science.gov (United States)

    Manzardo, Ann M; He, Jianghua; Poje, Albert; Penick, Elizabeth C; Campbell, Jan; Butler, Merlin G

    2013-12-01

    Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analog, benfotiamine (BF), and BF's effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria for current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, -611 ± 380 standard drinks; PL: N=11, -159 ± 562 standard drinks, p-value=0.02). BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Randomized, placebo-controlled, double-blind trial of Swedish snus for smoking reduction and cessation

    Directory of Open Access Journals (Sweden)

    Nilsson Robert

    2011-09-01

    Full Text Available Abstract Background Epidemiological studies suggest that smokeless tobacco in the form of Swedish snus has been used by many smokers in Scandinavia to quit smoking, but the efficacy of snus has so far not been evaluated in controlled clinical trials. Methods We conducted a randomized, double-blind, placebo-controlled, clinical trial aimed at assessing the efficacy of snus to help adult cigarette smokers in Serbia to substantially reduce, and, eventually, completely stop smoking. The study enrolled 319 healthy smokers aged 20-65 years at two occupational health centers in Belgrade, Serbia. Most of them (81% expressed an interest to quit rather than just reduce their smoking. Study products were used ad libitum throughout the 48-week study period. The main study objective during the first 24 weeks was smoking reduction. The primary end-point was defined as a biologically verified reduction of ≥ 50% in the average number of smoked cigarettes per day during week 21-24 compared to baseline. During week 25-48 participants were actively instructed to stop smoking completely. Outcome measures of biologically verified, complete smoking cessation included 1-week point prevalence rates at clinical visits after 12, 24, 36, and 48 weeks, as well as 4-, 12- and 24-week continued cessation rates at the week 36 and 48 visits. Results At the week 24 visit, the proportion of participants who achieved the protocol definition of a ≥ 50% smoking reduction was similar in the two treatment groups. However, the proportion that reported more extreme reductions (≥ 75% was statistically significantly higher in the snus group than in the placebo group (p Conclusions Swedish snus could promote smoking cessation among smokers in Serbia, that is, in a cultural setting without traditional use of oral, smokeless tobacco. Trial registration www.clinicaltrials.gov, identifier: NCT00601042

  9. Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

    Science.gov (United States)

    Mathie, Robert T; Clausen, Jürgen

    2015-09-15

    No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

  10. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

    Science.gov (United States)

    van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

    2017-08-01

    To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; ptofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. A double-blind study comparing ibuprofen 1800 mg or 2400 mg daily and placebo in sports injuries.

    Science.gov (United States)

    Hutson, M A

    1986-01-01

    In a double-blind, placebo-controlled study of forty-six patients with acute ligamentous damage of the knee, ibuprofen in dosages 1800 mg and 2400 mg produced significant improvements in joint mobility, weight bearing ability and match fitness. Joint effusion, pain on stress and pain severity was significantly improved by all three treatments. Only two patients reported side-effects (one while taking placebo and one taking ibuprofen 2400 mg). The study confirmed the efficacy and excellent tolerance to ibuprofen in patients with sports injuries to the knee.

  12. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial

    DEFF Research Database (Denmark)

    Lassen, Michael Rud; Raskob, Gary E; Gallus, Alexander

    2010-01-01

    efficacy and safety of these drugs after elective total knee replacement. METHODS: In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system......BACKGROUND: Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed...

  13. Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

    Science.gov (United States)

    Lee, Bonsan Bonne; Toh, Swee-Ling; Ryan, Suzanne; Simpson, Judy M; Clezy, Kate; Bossa, Laetitia; Rice, Scott A; Marial, Obaydullah; Weber, Gerard; Kaur, Jasbeer; Boswell-Ruys, Claire; Goodall, Stephen; Middleton, James; Tudehope, Mark; Kotsiou, George

    2016-04-16

    Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons

  14. The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions

    DEFF Research Database (Denmark)

    Anthon, Carl Thomas; Granholm, Anders; Perner, Anders

    2017-01-01

    INTRODUCTION: Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply......(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded