Selecting investigators for a placebo controlled clinical trial: The most critical decision point?

1997 ◽  
Vol 12 (S3) ◽  
pp. 261s-262s
Author(s):  
IA Niklson ◽  
PE Reimitz ◽  
C Sennef
Keyword(s):  
Antidepressant Treatment ◽  
Treatment Strategies ◽  
Patient Characteristics ◽  
Active Treatment Group ◽  
Drop Out ◽  
Controlled Clinical Trial ◽  
Decision Point ◽  
Double Blind ◽  
Psychotropic Compound ◽  
Post Hoc

Summary We have analysed the trial results obtained in two placebo and imipramine controlled double blind studies with a new psychotropic compound. Statistical analysis as outlined in the protocol showed a rather meagre therapeutic effect of imipramine of 1.53 points difference on HAMD-17 total score in comparison to placebo. In order to increase the discriminative power of the analysis we performed a post hoc analysis selecting centres that were able to detect a difference of at least two centres points between imipramine and placebo on HAMD-17 total score at week 6 (selective centres). All other were called nonselective. The analysis revealed that there were no statistically significant differences between the two types of centres concerning patient characteristics except that the nonselective centres recruited less patients with previous good response to antidepressant treatment. There was also some difference in drop out rates in the active treatment group wich might indicate different treatment strategies in the two groups of centres that participated in this trials.

scholarly journals Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Miao Miao ◽  
Xian Xiao ◽  
Jiayi Tian ◽  
Yunzhi Zhufeng ◽  
Ruiling Feng ◽  
...  
Keyword(s):  
Low Dose ◽  
Activity Index ◽  
Cell Subset ◽  
Immunoglobulin M ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Immune Balance ◽  
Cell Balance ◽  
Post Hoc

Abstract Objective To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial. Methods A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets. Results Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance. Conclusion These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance. Trial registration number ClinicalTrials.gov Registries (NCT02465580).

Hydromorphone extended release for neuropathic and non-neuropathic/nociceptive chronic low back pain: A post hoc analysis of data from a randomized, multicenter, double-blind, placebo-controlled clinical trial

2014 ◽  
Vol 10 (5) ◽  
pp. 311 ◽  
Author(s):  
Srinivas Nalamachu, MD ◽  
Martin Hale, MD ◽  
Arif Khan, MD
Keyword(s):  
Clinical Trial ◽  
Low Back Pain ◽  
Extended Release ◽  
Controlled Clinical Trial ◽  
Low Back ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Titration Phase ◽  
Post Hoc

Objective: The aim of this study was to determine the efficacy and tolerability of hydromorphone extended release (ER) in patients with chronic low back pain (LBP) with or without a neuropathic component.Design: This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled clinical trial using a randomized withdrawal design, performed in patients with moderate to severe chronic LBP. Patients achieving stable doses of hydromorphone ER during a 2- to 4-week conversion and titration phase were randomized to continue treatment with hydromorphone ER or taper-down to placebo during a 12-week double-blind phase. The primary efficacy outcome was the mean change in 11-point Numeric Rating Scale (NRS) pain intensity score from randomization to the final visit of the double-blind phase. Tolerability was assessed by recording adverse events (AEs). Data were analyzed separately for patients with non-neuropathic and neuropathic LBP.Results: A total of 173 patients with non-neuropathic/nociceptive LBP and 94 with neuropathic LBP were randomized into the double-blind phase. During the conversion and titration phase, mean (SD) NRS scores decreased significantly from 6.5 (1.87) and 6.4 (1.99) at screening to 3.3 (0.98) and 3.2 (1.05), respectively. For both LBP subgroups, patients randomized to hydromorphone ER maintained this improvement over the double-blind treatment period, whereas those randomized to placebo reported significant increase in NRS scores. Across subgroups, the incidence of 1 or more AE was 54 percent to 57 percent in the conversion and titration phase and 47 percent to 55 percent in the double-blind phase.Conclusions: The results of this study indicate that hydromorphone ER is efficacious and generally well tolerated in the management of patients with non-neuropathic and neuropathic chronic LBP.

Antipsychotic Effects of Cannabidiol

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
F.M. Leweke ◽  
D. Koethe ◽  
F. Pahlisch ◽  
D. Schreiber ◽  
C.W. Gerth ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Paranoid Schizophrenia ◽  
Treatment Strategies ◽  
Endocannabinoid System ◽  
Psychotic Symptoms ◽  
Controlled Clinical Trial ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Acute Schizophrenia

Background:In contrast to delta-9-tetrahydrocannabinol, the phytocannabinoid cannabidiol does not exert psychotomimetic effects. Cannabidiol was suggested a re-uptake inhibitor of anandamide and potential antipsychotic properties have been hypothesized for it. We therefore performed a clinical trial to investigate thesis hypothesis and to clarify the underlying link to the neurobiology of schizophrenia.Methods:We performed an explorative, 4-week, double-blind, controlled clinical trial on the effects of purified cannabidiol in acute schizophrenia compared to the antipsychotic amisulpride. The antipsychotic properties of both drugs were the primary target of the study. Furthermore, side-effects and anxiolytic capabilities of both treatments were investigated.Results:42 patients fulfilling DSM-IV criteria of acute paranoid schizophrenia participated in the study. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride.Conclusions:Cannabidiol revealed substantial antipsychotic properties in acute schizophrenia. This is in line with our suggestion of an adaptive role of the endocannabinoid system in paranoid schizophrenia, and raises further evidence that this adaptive mechanism may represent a valuable target for antipsychotic treatment strategies.The Stanley Medical Research Institute (00-093 to FML) and the Koeln Fortune Program (107/2000 + 101/2001 to FML) funded this study.

Diagnosis of Predominant Negative Symptoms: Post-hoc Analyses of a Phase 3 Clinical Trial with Cariprazine Monotherapy and Risperidone

2017 ◽  
Vol 41 (S1) ◽  
pp. S270-S270
Author(s):  
I. Laszlovszky ◽  
Á. Barabássy ◽  
E. Szalai ◽  
B. Szatmári ◽  
J. Harsányi ◽  
...  
Keyword(s):  
Patient Population ◽  
Negative Symptoms ◽  
Social Performance ◽  
Dose Range ◽  
Patient Characteristics ◽  
Phase 3 ◽  
Double Blind ◽  
Parallel Group ◽  
Baseline Values ◽  
Post Hoc

ObjectiveTo present, post hoc analyses from a controlled, prospective study of predominant negative symptoms (PNS) of schizophrenia on baseline patient characteristics, severity of symptoms and their variability among participating countries.MethodsData were analyzed from a phase 3, randomized, double-blind, active-controlled, parallel-group study in adult PNS patients with schizophrenia (EudraCT Number 2012-005485-36). Subjects with a PANSS factor score for negative symptoms (PANSS-FSNS) ≥ 24 and no pseudo-specific factors (e.g. high positive symptoms, extrapyramidal symptoms, depression) were randomized to cariprazine 4.5 mg/d (dose range: 3–6 mg/d) or risperidone 4 mg/d (dose range: 3–6 mg/d) for 26 weeks. Baseline values of PANSS-FSNS, individual PANSS items, personal and social performance (PSP), and clinical global impression of severity (CGI-S) were analyzed based on the data gained from 11 European participating countries.ResultsAverage PANSS-FSNS of patients was 27.6 ± 2.48, reflecting severe negative symptoms. Patients were moderately ill (CGI-S 4.2 ± 0.75), with marked difficulties (PSP 48.4 ± 10.78) predominantly in social functioning. The investigated patient population was fairly homogeneous as shown by small variability in all three scores. Moreover, baseline values in the 11 countries presented low variability while number of enrolled patients per country showed high variance (n = 7–118). Narrative description of symptoms and individual PANSS items rated as most severe and prominent were in high correlation.ConclusionPost hoc evaluation of this predominant negative symptom study showed that, this patient population can be identified reliably by psychiatrist. Additional training on the judgment of personal and social relationships can increase the diagnostic accuracy.Disclosure of interestEmployee of Gedeon Richter Plc.

scholarly journals Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain)

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025002 ◽  
Author(s):  
Daniel H Strauss ◽  
Divya R Santhanam ◽  
Samuel A McLean ◽  
Francesca L Beaudoin
Keyword(s):  
Chronic Pain ◽  
Rhode Island ◽  
Musculoskeletal Pain ◽  
Scientific Journal ◽  
Current Treatment ◽  
Drop Out ◽  
Chronic Musculoskeletal Pain ◽  
Controlled Clinical Trial ◽  
Double Blind

IntroductionChronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.Methods and analysisThe primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18–59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.Ethics and disseminationEthics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.Trial registration numberNCT03315533.

scholarly journals CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial

2010 ◽  
Vol 69 (11) ◽  
pp. 2013-2016 ◽  
Author(s):  
Arno W R van Kuijk ◽  
Clarissa E Vergunst ◽  
Danielle M Gerlag ◽  
Barry Bresnihan ◽  
Juan J Gomez-Reino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chemokine Receptor ◽  
Controlled Trial ◽  
Active Treatment Group ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Before And After ◽  
Trial Treatment ◽  
Ccr5 Blockade

ObjectiveC-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored.MethodsIn this phase Ib randomised, placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in patients with active RA was evaluated. Clinical efficacy was assessed using European League Against Rheumatism and American College of Rheumatology response criteria. ST biopsies were taken before and after 28 days of treatment, and analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were obtained before and after treatment.ResultsIn all, 32 patients were included; 20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did not complete the study due to adverse events; none of these were serious. No improvement was observed in the active treatment group compared to placebo. Results were consistent for clinical evaluation, ST analysis and MRI.ConclusionThis proof of concept study does not support the use of CCR5 blockade as a therapeutic strategy in patients with active RA.

scholarly journals Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine

CNS Spectrums ◽  
2017 ◽  
Vol 24 (03) ◽  
pp. 322-332 ◽  
Author(s):  
Claudio N. Soares ◽  
Min Zhang ◽  
Matthieu Boucher
Keyword(s):  
Functional Outcome ◽  
Functional Impairment ◽  
Antidepressant Treatment ◽  
Pooled Analysis ◽  
Study Endpoint ◽  
Double Blind ◽  
Early Improvement ◽  
Outcome Monitoring ◽  
Treatment Comparisons ◽  
Post Hoc

ObjectiveThis post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.MethodsData were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0–3), moderate (4–6), and marked/extreme (7–10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.ResultsGreater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001).ConclusionsTreatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.

Factors predicting the probability of relapse after discontinuation of migraine preventive treatment with topiramate

Cephalalgia ◽  
2010 ◽  
Vol 30 (11) ◽  
pp. 1290-1295 ◽  
Author(s):  
Jean Schoenen ◽  
Uwe Reuter ◽  
Hans-Christoph Diener ◽  
Joop Pfeil ◽  
Susanne Schwalen ◽  
...  
Keyword(s):  
Impact Test ◽  
Preventive Treatment ◽  
Patient Characteristics ◽  
Potential Contribution ◽  
Open Label ◽  
Double Blind ◽  
Predicting Factors ◽  
Acute Medication ◽  
Post Hoc ◽  
Headache Impact

Introduction: Demographic and clinical variables were examined in a post hoc analysis of the PROlonged Migraine Prevention with Topiramate (PROMPT) study to determine potential contribution to relapse. Methods: After a six-month open-label (OL) topiramate phase, patients were randomised to continue topiramate or switch to placebo in a six-month double-blind (DB) phase. ‘Relapse’ was investigated in terms of change in monthly migraine days after randomisation compared with the month before randomisation, and was analysed during the first (‘initial relapse’) and last month (‘sustained relapse’) of the DB phase. More than 40 potential predicting factors were entered into analyses of variance and covariance. Results: For initial relapse, variable-by-treatment interactions were significant for the Headache Impact Test (HIT-6) at DB baseline, and decline in acute medication intake or reporting of ‘anxiety’ in the OL phase. For sustained relapse, no statistically significant interactions were observed. Conclusion: Relapse after topiramate discontinuation in migraine prophylaxis appears to be unaffected by patient characteristics or baseline migraine frequency.

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