NIH-funded study reveals treatment does not show benefit over placebo following head injury
Results of a phase 3 randomized, placebo-controlled clinical trial suggest that progesterone may not significantly improve outcomes in patients who have suffered a moderate to severe traumatic brain injury. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. The findings were published in the New England Journal of Medicine.
The Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment trial (ProTECT- III) study took place at 49 trauma centers across the United States that are part of the NINDS Neurological Emergencies Treatment Trials Network. Eight hundred and eighty two patients were randomized to receive progesterone or placebo within four hours of sustaining their head injury and continued to receive the intervention for 96 hours. Study participants were closely followed by researchers for six months. The main outcome of this study was functional recovery of disability at six months after head injury.
The researchers had originally planned to enroll 1140 subjects, but the trial was stopped early following a safety review. The data analyzed at that point indicated that there was no benefit to administering progesterone treatment after head injury.
When researchers compared the treatments, they found that clinical improvement occurred in 51 percent of patients who received progesterone and 56 percent of patients who received placebo, indicating that progesterone alone did not improve their injury-related disability compared to standard medical therapy.
“The results are a wakeup call to our current approach to drug development and translation of preclinical evidence of neuroprotection and TBI,” said David W. Wright, M.D., Director of Emergency Neurosciences at Emory University School of Medicine in Atlanta, Georgia and lead author of this study.
Progesterone is a hormone that is found in the brains of males and females, but is primarily associated with pregnancy. Prior to this research, animal studies showed that progesterone appeared to help improve recovery and reduce the extent of brain damage following traumatic head injury. In addition, small clinical trials suggested that progesterone might be beneficial after head injury.
"The trial results were not what we had hoped. Scientists must now redouble their efforts to develop treatments that protect the brain and enhance its natural recovery mechanisms. Most importantly we need to aggressively pursue whether or not the drugs showing promise in animal studies can achieve the desired biologic effect in people before moving to late stage trials. Without such indicators we never learn whether we chose the right dose, duration or even the right drug." said Walter Koroshetz, M.D., director of NINDS.
Dr. Wright and his colleagues suggest that in order to improve results of clinical trials, cutting-edge research techniques need to be developed, including animal studies that will better predict outcomes of human trials.
“As we move forward, we need to completely overhaul of the process of clinical trial design. We need a radically new approach for reviewing how drugs are assessed in animals, how drugs are prepared for human trials and how trials themselves are designed,” said Dr. Wright.
This study was supported by grants from NINDS (NS062778, NS059032, NS056975).
- by Barbara I. McMakin
Article:
Wright et al. “Very Early Administration of Progesterone for Acute Traumatic Brain Injury,” New England Journal of Medicine, December 11, 2014, DOI: 10.1056/NEJMoa1404304
Please visit NINDS Traumatic Brain Injury information page for more information.
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The NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov.