Suicide concerns prompt early termination of rimonabant trial

A study evaluating the cardiovascular outcomes related to rimonabant was discontinued because of concerns regarding the risk of suicide associated with the weight-loss drug, according to a report in the Aug. 14 issue of The Lancet, as reported by HealthDay News.

A study evaluating the cardiovascular outcomes related to rimonabant was discontinued because of concerns regarding the risk of suicide associated with the weight-loss drug, according to a report in the Aug. 14 issue of The Lancet, as reported by HealthDay News.

In the double-blind, placebo-controlled, rimonabant for prevention of cardiovascular events (CRESCENDO) trial, Eric J. Topol, MD, of the Scripps Translational Science Institute in La Jolla, Calif., and colleagues randomly assigned 18,695 patients with an increased or previously manifest risk of vascular disease to receive either rimonabant 20 mg or placebo.

The authors said the trial was prematurely terminated after a mean follow-up of 13.8 months, as health regulatory authorities in 3 countries were concerned with the risk of suicide in individuals taking rimonabant.

Among study participants, 4 patients receiving rimonabant and 1 patient receiving placebo committed suicide. Upon discontinuation of the trial on Nov. 6, 2008, investigators found that the composite primary end point of cardiovascular death, myocardial infarction, or stroke occurred in 3.9% of patients receiving rimonabant and 4.0% receiving placebo (P=.68).

Compared with patients receiving placebo, gastrointestinal, neuropsychiatric, and serious psychiatric adverse effects significantly increased in patients receiving rimonabant.

“The findings did not provide evidence of efficacy for rimonabant’s prevention of adverse cardiovascular outcomes, but further substantiated its effect of inducing serious neuropsychiatric side effects,” the authors wrote.

“It doesn’t look like we can do anything to ‘rescue’ rimonabant since we do not have access to the DNA of those individuals who suffered serious neuropsychiatric side effects,” Dr Topol told Formulary. He added, however, that one of the lessons learned from the CRESCENDO trial is the importance of collecting such samples. “There have been several recent breakthroughs in pharmacogenomics that are quite encouraging for the future of drug development,” he said.

The study was funded by Sanofi-Aventis.