MANHASSET, NY – Raj K. Narayan, MD, and Brett E. Skolnick, PhD, are among the authors of a paper published today on a clinical trial of progesterone for severe traumatic brain injury (TBI).
The study concluded that there were no clinical benefits after five days of treatment with a novel formulation of progesterone acutely administered to patients with TBI.
“A Clinical Trial of Progesterone for Severe Traumatic Brain Injury,” was published online by The New England Journal of Medicine, Dec. 10 (print version to appear, Dec. 25). The study was funded by BHR Pharma.
“This trial, referred to as SyNAPSe, reports on a large prospective randomized clinical trial that investigated the effects of progesterone administered to severe TBI patients,” said Dr. Narayan, executive director of North Shore-LIJ’s Cushing Neuroscience Institute. “Despite extensive experimental support in numerous animal models, as well as very promising preliminary data from smaller single center trials, this Phase III study failed to show benefit of progesterone in severe TBI,” said Dr. Narayan.
In this multinational, placebo-controlled trial, 1195 patients, 16-70 years of age, with severe TBI were randomly assigned to receive progesterone or placebo. Dosing began within eight hours after injury and continued for 120 hours. Analysis showed no treatment effect of progesterone as compared with placebo. The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (the combination of patients with good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality rates in both groups were the same and there were no relevant safety signal differences between progesterone and placebo.
“The trial suggests that although promising agents may be found in early experiments, the selection process may still lack the precision for ultimately identifying agents with clinical benefit for this devastating and common disorder for which no proven pharmacological therapies exist,” said Dr. Skolnick, adjunct associate professor of neurosurgery at the Hofstra North Shore-LIJ School of Medicine. “It also highlights the difficulty in demonstrating the efficacy of any drug in this complex disease since the outcome may be affected by many factors. Animal models usually replicate only one aspect of the injury, but human TBI patients can suffer multiple medical and surgical problems that can affect their ultimate outcome.”
Despite this disappointment, Dr. Narayan and Dr. Skolnick said they were proud to have been involved in the successful conduct of this large and complex trial, which was executed with great scientific rigor across many centers and continents. The need to find better treatments for this severe injury remains as great as ever and what we have learned from this trial will help us better design future trials.
For more information about North Shore-LIJ’s Traumatic Brain Injury Center, call 516/562-3816.