After five days of treatment with a novel formulation of progesterone acutely administered to patients with severe traumatic brain injury, the study concluded that it showed no clinical benefits.
The paper entitled, "A Clinical Trial of Progesterone for Severe Traumatic Brain Injury," will be published online in The New England Journal of Medicine
, December 10, 2014.
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 Raj K. Narayan, MD, executive director, North Shore-LIJ's Cushing Neuroscience Institute and one of the co-authors of the paper. "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."
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 Brett E. Skolnick, PhD, adjunct associate professor of neurosurgery at the Hofstra North Shore-LIJ School of Medicine and who served as lead author of the paper.
"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. 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."