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Double-blind Trials (double-blind + trials)
Selected AbstractsNicotine as an Antiepileptic Agent in ADNFLE: An N-of-One StudyEPILEPSIA, Issue 9 2003John O. Willoughby Summary:,Purpose: To test nicotine patch treatment for a patient with a defined mutation for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) whose seizures were refractory to standard antiepileptic therapy. Methods: Open and double-blind trials of nicotine patches in an "n-of-one" study. The double-blind trial comprised periods during which either placebo or nicotine patches were each used for three periods of 2 weeks, randomized in a double-blind manner. Results: In an open study, nicotine patches reduced seizures from 1.65 ± 2.36 to 0.01 ± 0.0 seizures per day (p < 0.0001). In a double-blinded placebo-controlled phase, the average frequency of seizures on nicotine versus placebo was 0 ± 0 versus 0.56 ± 1.14 seizures per day (p < 0.0001). Conclusions: Nicotine patches may be of benefit to some individuals with ADNFLE. [source] Trospium chloride once-daily extended release is effective and well tolerated for the treatment of overactive bladder syndrome: an integrated analysis of two randomised, phase III trialsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2009D. R. Staskin Summary Background:, Trospium chloride is an antimuscarinic agent with a hydrophilic polar quaternary amine structure that is minimally metabolised by hepatic cytochrome P450 and is actively excreted in the urine, each of which confers a potential benefit with regard to efficacy and tolerability. Purpose:, We analysed pooled data from two identically designed phase III trials of a once-daily, extended-release (XR) formulation of trospium chloride (trospium XR 60-mg capsules) in subjects with overactive bladder syndrome (OAB). Methods:, Adults with OAB of , 6 months' duration with urinary urgency, frequency and , 1 urge urinary incontinence (UUI) episode/day were enrolled in these multicentre, parallel-group, double-blind trials. Participants were randomised (1 : 1) to receive trospium XR 60 mg or placebo for 12 weeks. Primary efficacy variables were changes in urinary frequency and the number of UUI episodes/day. Adverse events (AEs) were recorded throughout. Results:, In total, 1165 subjects were randomised (trospium XR, 578; placebo, 587). At baseline, subjects averaged 12.8 toilet voids/day and 4.1 UUI episodes/day. Compared with placebo, subjects treated with trospium XR had significantly greater reductions from baseline in the mean number of toilet voids/day (,1.9 vs. ,2.7; p < 0.001) and UUI episodes/day (,1.8 vs. ,2.4; p < 0.001) at week 12. The most frequent AEs considered possibly related to study treatment were dry mouth (trospium XR, 10.7%; placebo, 3.7%) and constipation (trospium XR, 8.5%; placebo, 1.5%). Notably, rates of central nervous system (CNS) AEs were lower with trospium XR vs. placebo (dizziness: 0.2% vs. 1.0%; headache: 1.4% vs. 2.4%). Conclusions:, Treatment with trospium XR resulted in statistically significant improvements in both of the dual primary and all of the secondary outcome variables. Trospium XR demonstrated favourable rates of AEs, particularly CNS AEs (numerically lower than with placebo) and dry mouth (lower than previously reported with trospium immediate-release, although not compared in a head-to-head study). [source] Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 yearsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008C. A. Dujovne Summary Aims:, This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). Methods:, Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3,5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. Results:, The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of , 3-fold consecutive elevations of liver transaminases (0.7%) or , 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of ,18% were maintained throughout the study. Conclusions:, Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction. [source] Duloxetine 60 mg once daily in the treatment of milder major depressive disorderINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2006D. G. S. Perahia Summary There is ongoing debate regarding the effectiveness of antidepressants in patients with milder major depressive disorder (MDD). This post-hoc analysis evaluated the efficacy and tolerability of duloxetine in the subset of 159 (75 duloxetine and 84 placebo) patients with milder MDD (baseline HAMD17 total score ,15 and ,18) who were treated once daily with duloxetine 60 mg or placebo in two identical, 9-week, randomised, double-blind trials. At endpoint, change from baseline on HAMD17 was greater in the duloxetine group (,7.0) than in the placebo group (,4.1) (p = 0.005). Response and remission rates, and improvement on the Clinical Global Impressions-Severity (CGI-S) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and measures of painful symptoms were also significantly better in the duloxetine group (p < 0.05). Tolerability was consistent with that seen in previous studies of duloxetine in patients with more severe depression. In conclusion, duloxetine 60 mg/day is effective and well tolerated in milder MDD. [source] Cultural Variations in the Placebo Effect: Ulcers, Anxiety, and Blood PressureMEDICAL ANTHROPOLOGY QUARTERLY, Issue 1 2000Daniel E. Moerman An analysis of the control groups in double-blind trials of medicines demonstrates broad variation,from 0 to 100 percent,in placebo effectiveness rates for the same treatment for the same condition. In two cases considered here, drug healing rates covary with placebo healing rates; placebo healing is the ultimate and inescapable "complementary medicine. " Several factors can account for the dramatic variation in placebo healing rates, including cultural ones. But because variation differs by illness, large placebo effects for one condition do not necessarily anticipate large placebo effects for other conditions as well. Deeper understanding of the intimate relationship between cultural and biological processes will require close ethnographic scrutiny of the meaningfulness of medical treatment in different societies, [placebo effect, ulcer disease, anxiety, hypertension, cross-cultural variation] [source] The pharmacological treatment for uremic restless legs syndrome: Evidence-based review,MOVEMENT DISORDERS, Issue 10 2010Márcio Moysés de Oliveira MD Abstract Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthesis of the evidence is needed in order to evaluate the effectiveness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double-blind trials on treatments for uremic RLS. The outcomes considered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life measured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg movement while asleep in the treatment group. No combined analysis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few therapeutic trials on patients with uremia with RLS have been published, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Therapy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed. © 2010 Movement Disorder Society [source] Indinavir did not further increase mean triglyceride levels in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors: An analysis of three randomized clinical trialsPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2003Carlos Rojas MD Abstract Objectives Metabolic abnormalities including hyperlipidemia have developed in patients infected with the human immunodeficiency virus (HIV) after treatment with protease inhibitor drugs. It is unclear whether the deleterious effects on plasma triglyceride concentrations observed in patients receiving highly active antiretroviral therapy are a class effect of protease inhibitors. Hypertriglyceridemia may constitute a risk factor for cardiovascular disease. The purpose of this retrospective analysis of HIV-infected patients enrolled in three randomized, double-blind trials of indinavir therapy was to determine whether indinavir use was associated with a larger increase in triglyceride levels than treatment without a protease inhibitor. Methods Using a mixed-effects model, we compared average changes in nonfasting plasma triglyceride levels among randomized treatment groups for each protocol separately. Results The median increase in triglyceride levels during the 1st year of antiretroviral monotherapy was less with indinavir than with either zidovudine or stavudine. The combination of indinavir and nucleoside-analogue reverse-transcriptase inhibitors (NRTI) resulted in smaller increments in triglyceride levels than NRTI monotherapy. Indinavir also augmented the reduction in triglyceride levels observed with combination therapy using zidovudine and lamivudine in persons with far advanced HIV-infection. However, up to 7% of patients receiving a NRTI and indinavir experienced elevations of nonfasting triglyceride levels in excess of 750,mg/dl. Conclusions On average, the combination of indinavir and NRTI therapy was not associated with a greater elevation of non-fasting triglyceride levels in HIV-infected men with at least moderately advanced immunosuppression than treatment with NRTI drugs alone. Copyright © 2003 John Wiley & Sons, Ltd. [source] Asenapine versus olanzapine in acute mania: a double-blind extension studyBIPOLAR DISORDERS, Issue 8 2009Roger S McIntyre Objective:, To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania. Methods:, Patients with bipolar I disorder experiencing acute manic or mixed episodes who completed either of two 3-week, double-blind trials with asenapine 5 or 10 mg twice daily, olanzapine 5 to 20 mg once daily, or placebo were eligible for this 9-week, double-blind extension study. Patients receiving active medication in the 3-week trials continued the same regimen; those who had received placebo were blindly switched to asenapine but were assessed for safety outcomes only. The primary efficacy measure was the change from baseline to day 84 on the Young Mania Rating Scale (YMRS) total score in the per-protocol population. Results on the primary efficacy outcome were used to determine the noninferiority of asenapine versus olanzapine. Results:, A total of 504 patients (placebo/asenapine, n = 94; asenapine, n = 181; olanzapine, n = 229) were enrolled in the extension study. At day 84, the mean (SD) change from baseline in YMRS total score was ,24.4 (8.7) for asenapine and ,23.9 (7.9) for olanzapine. Prespecified statistical analysis for noninferiority indicated no significant difference between asenapine and olanzapine. The overall incidence of treatment-emergent adverse events was similar across treatment groups (77% placebo/asenapine, 77% asenapine, 78% olanzapine). Clinically significant weight gain occurred in 10%, 19%, and 31% of the placebo/asenapine, asenapine, and olanzapine groups, respectively. Conclusions:, Asenapine was efficacious, showed noninferiority to olanzapine, and was well tolerated in the extended treatment of patients experiencing manic symptoms associated with bipolar I disorder. [source] Topiramate in painful diabetic polyneuropathy: findings from three double-blind placebo-controlled trialsACTA NEUROLOGICA SCANDINAVICA, Issue 4 2004The Topiramate Diabetic Neuropathic Pain Study Group Objectives , To evaluate the efficacy and tolerability of topiramate in patients with painful diabetic polyneuropathy. Materials and methods , Patients with moderate to extreme pain (0,4 Categorical Pain Scale score , 2) were randomized to placebo or topiramate (100, 200, or 400 mg/day) in three similar double-blind trials. The primary efficacy analysis was pain reduction from final visit to baseline in the 100-mm Visual Analog Scale (VAS) for the intent-to-treat populations. Results , After 18,22 weeks of double-blind treatment, pain reductions were numerically greater with topiramate in two studies but differences between topiramate and placebo in VAS scores or in the secondary efficacy endpoints did not reach statistical significance in any of the three studies. Across all studies, 24% of topiramate-treated patients and 8% of placebo-treated patients discontinued due to adverse events; groups did not differ in the occurrence of serious adverse events. Conclusion , These studies did not find topiramate to be significantly more effective than placebo in reducing pain scores in patients with painful diabetic polyneuropathy. Several design features may have precluded the studies from having sufficient sensitivity to differentiate effective and ineffective treatments. The study design and results are instructive for other investigators designing future clinical studies in neuropathic pain. [source] | ||||||||||