Rivaroxaban for Preventing Venous Thromboembolism in High-Risk Ambulatory Patients with Cancer: Rationale and Design of the CASSINI Trial. Rationale and Design of the CASSINI Trial.

Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).

Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multisite randomized controlled trial.

BACKGROUND: Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating gamma-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being. METHODS: In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy. RESULTS: Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels-effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease. Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo. CONCLUSION: Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.

Topiramate for treating alcohol dependence: a randomized controlled trial.

CONTEXT: Hypothetically, topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol's reinforcing effects through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system. OBJECTIVE: To determine if topiramate is a safe and efficacious treatment for alcohol dependence. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled, 14-week trial of 371 men and women aged 18 to 65 years diagnosed with alcohol dependence, conducted between January 27, 2004, and August 4, 2006, at 17 US sites. INTERVENTIONS: Up to 300 mg/d of topiramate (n = 183) or placebo (n = 188), along with a weekly compliance enhancement intervention. MAIN OUTCOME MEASURES: Primary efficacy variable was self-reported percentage of heavy drinking days. Secondary outcomes included other self-reported drinking measures (percentage of days abstinent and drinks per drinking day) along with the laboratory measure of alcohol consumption (plasma gamma-glutamyltransferase). RESULTS: Treating all dropouts as relapse to baseline, topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 (mean difference, 8.44%; 95% confidence interval, 3.07%-13.80%; P = .002). Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days (mean difference, 16.19%; 95% confidence interval, 10.79%-21.60%; P < .001) and all other drinking outcomes (P < .001 for all comparisons). Adverse events that were more common with topiramate vs placebo, respectively, included paresthesia (50.8% vs 10.6%), taste perversion (23.0% vs 4.8%), anorexia (19.7% vs 6.9%), and difficulty with concentration (14.8% vs 3.2%). CONCLUSION: Topiramate is a promising treatment for alcohol dependence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00210925.

Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study.

BACKGROUND: In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial. METHODS: Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized. RESULTS: A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate. CONCLUSIONS: This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.