scholarly journals The place of S-ketamine in fibromyalgia treatment (ESKEFIB): study protocol for a prospective, single-center, double-blind, randomized, parallel-group, dose-escalation controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zuzana Javorcikova ◽  
Michel Dangoisse ◽  
Stéphane Nikis ◽  
Jean-Paul Lechat ◽  
Aline Gillain ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Relief ◽  
Dose Escalation ◽  
Primary Outcome ◽  
High Dose ◽  
Single Center ◽  
Double Blind ◽  
Link Type ◽  
Parallel Group

Abstract Background Fibromyalgia is a chronic multidimensional pain disease with no curative treatment currently available. Its management relies on a multimodal approach involving pharmacologic and non-pharmacologic elements. Because a suggested factor in its etiology is a central sensitization phenomenon involving the N-methyl-D-aspartate receptor (NMDAR), NMDAR antagonists have been proposed as a treatment target. Ketamine and its levogyre form, S-ketamine, have been used to treat chronic pain for many years without consensus about their therapeutic efficiency. We aim to assess the efficacy of S-ketamine as a co-treatment for fibromyalgia. Methods This prospective, randomized, single-center, double-blind, parallel-group, dose-escalation trial will compare a co-treatment with S-ketamine (intervention) to a control treatment without S-ketamine (control). It will consist of two successive cohorts with 2:1 randomization ratio (S-ketamine at two different doses: control) with 105 participants in each cohort. The protocol follow-up time will be 12 weeks, including 3 visits for the treatment (week 0, week 2, and week 4) and 3 visits for follow-up (week 6, week 9, and week 12). Our primary outcome, pain relief and/or better patient function, will be assessed with the Brief Pain Inventory questionnaire. The statistical analysis will be performed on an intention-to-treat basis. If the primary outcome is reached at the end of follow-up in the first cohort with low-dose S-ketamine (0.2 mg/kg), the trial will end. If not, the trial will continue with the second cohort and high-dose S-ketamine (0.4 mg/kg). Discussion The challenge of our trial is the inclusion of a large number of participants in comparison to other trials involving ketamine or S-ketamine infusions for chronic pain management. The originality of our protocol is to include functionality in addition to pain relief as a primary outcome because these two endpoints are not linked in a linear way. For some patients, functional status is more important than pain relief. Trial registration EudraCT reference: 2020-000473-25, ClinicalTrials.gov: NCT04436250, first posted June 18, 2020; last updated July 21, 2020. Protocol version 2.2 issued on September 30, 2020, after a revision by the ethics committee. https://clinicaltrials.gov/ct2/show/NCT04436250

Neuroleptic rotation for refractory agitation in cancer patients with delirium in the acute palliative care unit: A double-blind randomized clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12006-12006
Author(s):  
David Hui ◽  
Allison De La Rosa ◽  
Annie Wilson ◽  
Thuc Nguyen ◽  
Jimin Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Patients ◽  
Dose Escalation ◽  
Primary Outcome ◽  
Rotation Group ◽  
Dose Titration ◽  
Combination Group ◽  
Double Blind ◽  
Parallel Group ◽  
Group Randomized Trial

12006 Background: Terminal agitation commonly occurs in the last days of life and is highly distressing. The role of neuroleptics is controversial and few studies have examined agitation as a primary outcome. We assessed the effect of 3 neuroleptic strategies on refractory agitation in cancer patients with terminal delirium. Methods: In this single-center, double-blind, double-dummy parallel group randomized trial, patients admitted to a palliative and supportive care unit with refractory agitation despite low dose haloperidol were randomized in a 1:1:1 ratio to (1) haloperidol dose escalation, (2) neuroleptic rotation to chlorpromazine, or (3) combined haloperidol and chlorpromazine. Intravenous medications at equivalent doses were scheduled every 4 h and every 1 h as needed until discharge. The primary outcome was change in Richmond Agitation Sedation Scale (RASS) from time 0 to 24 hours. With 15 patients per group and 13 measurements over time, we had 90% power to detect an effect size of 0.2 with alpha=2.5%. One way ANOVA was used to examine within group differences. We also compared among groups with the Wilcoxon rank sum test. Results: 68 patients were enrolled and 45 received the blinded study interventions. The median survival was 73 h (95% CI 49, 106 h). RASS decreased significantly within 30 minutes and remained low at 24 hours in the dose escalation group (mean RASS change between 0 and 24 h [95% CI]: -3.6 [-5, -2.2]) v. rotation group (-3.3 [-4.4, -2.2]) v. combination group (-3 [-4.6, -1.4]), with no difference among groups (P=0.71). A majority of patients were perceived to be more comfortable after treatment by blinded caregivers (escalation v. rotation v. combination: 62% v. 71% v. 60%; P=0.83) and bedside nurses (64% v. 75% v. 64%; P=0.82); however, the rotation group had significantly fewer breakthrough restlessness (escalation v. rotation v. combination: 73% v. 19% v. 50%; P=0.009), required fewer upward dose titration (escalation v. rotation v. combination: 27% v. 6% v. 50%; P=0.03) and required less rescue neuroleptics in the first 24 hours (haloperidol equivalent: 4 mg vs. 2 mg vs. 6 mg, P=0.09, trend only). Hypotension was more frequently observed with chlorpromazine. Overall survival did not differ (>0.99). Conclusions: Preliminary data from this study supported that all 3 strategies of neuroleptics reduced agitation and improved comfort in patients with terminal delirium; however, neuroleptic rotation provided better agitation control and confirmatory studies are needed. Clinical trial information: NCT03021486 .

scholarly journals Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047993
Author(s):  
Nirosen Vijiaratnam ◽  
Christine Girges ◽  
Grace Auld ◽  
Marisa Chau ◽  
Kate Maclagan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Outcome ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Link Type ◽  
South Central ◽  
Disease Modifying ◽  
Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

scholarly journals Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sander Rozemeijer ◽  
Harm-Jan de Grooth ◽  
Paul W. G. Elbers ◽  
Armand R. J. Girbes ◽  
Corstiaan A. den Uil ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Vitamin C ◽  
Organ Failure ◽  
Controlled Trial ◽  
Lung Injury Score ◽  
High Dose ◽  
Double Blind ◽  
Link Type ◽  
Search Trial ◽  
Intravenous Vitamin

Abstract Background High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. Methods This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Discussion Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. Trial registration ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL

A Double-Blind Comparison of 0.25% and 0.05% Desoxymethasone, 0.1% Betamethasone Valerate and 1% Hydrocortisone Creams in the Treatment of Eczema

1987 ◽  
Vol 15 (3) ◽  
pp. 160-166 ◽  
Author(s):  
R. E. Ashton ◽  
M. Catterall ◽  
N. Morley ◽  
G. Fairris ◽  
D. N. Joseph
Keyword(s):  
Adverse Effects ◽  
Physical Properties ◽  
Effective Treatment ◽  
The Other ◽  
Betamethasone Valerate ◽  
Clinical Parameters ◽  
Double Blind ◽  
Parallel Group ◽  
Blind Comparison

The efficacy and acceptability of 0.25% and 0.05% desoxymethasone, 0.1% betamethasone valerate and 1% hydrocortisone creams were compared in patients with eczema. A double-blind parallel group multi-centre design was employed in which 96 patients were recruited by four centres. Patients used one cream for a 3-week period and follow-up assessment visits were made at weekly intervals. Efficacy variables were: erythema/redness, scaling, itching and extent of area affected. These variables were assessed by both the investigator and the patient. The 0.25% desoxymethasone was the most effective treatment, producing the greatest degree of improvement in all clinical parameters, hydrocortisone was the least effective and 0.05% desoxymethasone was of intermediate effectiveness. The 0.1% betamethasone produced similar results to 0.25% desoxymethasone for half the assessments; for the other half the results were similar to 0.05% desoxymethasone. No adverse effects were reported during the study. The results are discussed in terms of physical properties of the vehicles and corticosteroid potency.

scholarly journals One Year Follow-up of a Randomized, Double-Blind, Placebo-Controlled Trial of Percutaneous Peripheral Nerve Stimulation for Chronic Neuropathic Pain Following Amputation

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Joshua M Rosenow ◽  
Christopher Gilmore ◽  
Brian M Ilfeld ◽  
Sean Li ◽  
Mehul J Desai ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Relief ◽  
Peripheral Nerve ◽  
Nerve Stimulation ◽  
Peripheral Nerve Stimulation ◽  
Pain Interference ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo

Abstract INTRODUCTION Over 85% of patients experience residual limb (RLP) and/or phantom limb (PLP) pain following amputation. Peripheral nerve stimulation (PNS) is a non-opioid approach to relieve postamputation neuropathic pain. A recent multicenter, randomized, double-blind, placebo-controlled study using a novel percutaneous PNS system demonstrated clinically and statistically significant improvements in pain and pain interference with PNS compared to placebo (Gilmore et al, 2019). This work presents prospective 1-yr follow-up to assess durability of pain relief and functional improvements. METHODS Over 85% of patients experience residual limb (RLP) and/or phantom limb (PLP) pain following amputation. Peripheral nerve stimulation (PNS) is a non-opioid approach to relieve post-amputation neuropathic pain. A recent multicenter, randomized, double-blind, placebo-controlled study using a novel percutaneous PNS system demonstrated clinically and statistically significant improvements in pain and pain interference with PNS compared to placebo (Gilmore et al, 2019). This work presents prospective one-year follow-up to assess durability of pain relief and functional improvements. RESULTS A significantly greater proportion of subjects who completed the 12-mo visit reported = 50% pain relief on the BPI-SF (5/8, 63%; average pain relief = 73% among responders) compared to the placebo group at the time of crossover (0/14, 0%, P = .003; average pain relief = 23%). A majority of subjects also reported = 50% reductions in pain interference at 12 mo (5/8, 63%). Two of 13 (15%) subjects in the placebo group reported sustained improvements in pain interference (P = .06). Average reduction in pain interference among responders in the PNS group was 87%. CONCLUSION This work suggests that PNS delivered over 60 d may provide clinically significant and enduring pain relief, enabling improved function and potentially reducing the need for a permanently implanted system.

scholarly journals Evaluating the use of benzodiazepines following recent bereavement

2001 ◽  
Vol 178 (1) ◽  
pp. 36-41 ◽  
Author(s):  
James Warner ◽  
Chris Metcalfe ◽  
Michael King
Keyword(s):  
Primary Outcome ◽  
Outcome Measure ◽  
Primary Outcome Measure ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Negative Effect ◽  
Controlled Evaluation ◽  
Current Advice

BackgroundThere is no evidence to support current advice not to use benzodiazepines after bereavement.AimsTo determine the role of benzodiazepines in the management of bereavement.MethodWe conducted a randomised, double-blind, placebo-controlled evaluation of the use of diazepam after recent bereavement. Participants were randomised to either 2 mg diazepam or identically packaged placebo up to three times daily. The primary outcome measure was the Bereavement Phenomenology Questionnaire.ResultsThirty subjects were randomised. No evidence was found of an effect of benzodiazepines on the course of the first 6 months of bereavement (estimated mean difference of combined follow-up assessments=0.3 in favour of placebo; 95% CI –6.2 to +6.7).ConclusionWe found no evidence of a positive or negative effect of benzodiazepines on the course of bereavement.

scholarly journals Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2198-2206 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Olivier Rascol ◽  
Robert A. Hauser ◽  
Susan Huyck ◽  
Anjela Tzontcheva ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Active Control ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Parallel Group ◽  
Number Of Patients ◽  
Disease Rating ◽  
Post Hoc

Objective:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.Methods:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).Results:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).Conclusions:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.Clinical trial registration:Clinicaltrials.gov: NCT01155479.Classification of evidence:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

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