Patients in the naltrexone-bupropion group also experienced more adverse events, including gastrointestinal events (14.2% vs 1.9%; P<.001) and central nervous system symptoms (5.1% vs 1.2%; P<.001).
“Among overweight or obese patients at increased cardiovascular risk, based on the interim analyses performed after 25% and 50% of planned events, the upper limit of the 95% confidence interval of the HR for MACE for naltrexone-bupropion treatment, compared with placebo, did not exceed 2.0,” the researchers concluded.
“However, because of the unanticipated early termination of the trial, it is not possible to assess noninferiority for the prespecified upper limit of 1.4,” they added.
‘A Valuable Reminder’
Ultimately, the researchers noted that LIGHT may serve as a cautionary tale and could help guide future studies.
“The events leading to the termination of the study serve as a valuable reminder of the importance of maintaining confidentiality during ongoing trials. Premature release of interim data can result in inappropriate prejudgment about the benefits or risks of the studied therapy and make completion of the trial highly problematic,” they wrote.
“An FDA guidance for industry explicitly states that interim data from an ongoing clinical trial should remain confidential and warns that ‘such knowledge can bias the outcome of the study by inappropriately influencing its continuing conduct or the plan of analyses.'”
In an accompanying editorial, Joshua M. Sharfstein, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and Bruce M. Psaty, MD, PhD, of the University of Washington in Seattle, praised Dr Nissen and colleagues for conducting a meticulous, carefully reported study, but said that “the available data are difficult to interpret and therefore largely uninformative.”
“As more data on major adverse cardiovascular events accumulated after the first 25% of the expected outcome, the treatment group experienced more strokes, more myocardial infarctions, and greater overall mortality than the placebo group,” they wrote.
“The change in point estimates from 0.59 toward the null and the increase in the upper bound of the confidence interval as more data were analyzed clearly illustrate why caution is required in interpreting interim results.”
The study was sponsored by Orexigen Therapeutics Inc and Takeda Pharmaceuticals International.
- Nissen SE, Wolski KE, Prcela L, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA. 2016;315(10):990-1004. doi:10.1001/jama.2016.1558.
- Sharfstein JM, Psaty BM. Evaluation of the Cardiovascular Risk of Naltrexone-Bupropion: A Study Interrupted. JAMA. 2016;315(10):984-986. doi:10.1001/jama.2016.1461.