Despite promising preliminary research, a new study published in The New England Journal of Medicine indicates progesterone provides no improvement in clinical outcome for severe traumatic brain injury (TBI) patients.
“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.”
The study randomly assigned progesterone or a placebo to 1,195 patients between the ages of 16 and 7o with severe TBI. The patients received progesterone within eight hours after injury and continued for 120 hours.
The researchers saw no difference in the proportion of patients with more favorable outcomes when using the Glasgow Outcome Scale. According to the report 50.4% experienced good recoveries with progesterone, compared to 50.4% with placebo treatments. There was also no difference in mortality rates and no significant adverse safety effects.
“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,” added Skolnick.