Progesterone Offers No Significant Benefit after Traumatic Brain Injury

March 4, 2015

Treatment of acute traumatic brain injury with the hormone progesterone provides no significant benefit to patients, a National Institutes of Health-funded phase III clinical trial has concluded. The results were published recently in the New England Journal of Medicine. Banner – University Medical Center Tucson was one of 49 trauma centers that participated in the study.

The study, named ProTECT III (Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment), was conducted across the United States between July 2009 and November 2013. The Arizona hub had five “spokes” that, in addition to the Banner – University Medical Center Tucson and Banner – University Medical Center Phoenix, included Maricopa Medical Center, Scottsdale Healthcare Osborn Medical Center and University of New Mexico Hospital. The study originally was planned to include 1,140 patients, but was stopped after 882 patients because there was no significant difference in patient survival or favorable outcomes in the progesterone-treated group versus the placebo-treated group. The Arizona hub enrolled a total of 96 patients.

Favorable outcomes occurred in 51 percent of those who received progesterone and 56 percent of those who received placebo. Mortality after six months was 18.8 percent for progesterone and 15.7 percent for placebo.

“As an emergency physician who takes care of people with traumatic brain injury every day, it’s a terrible problem and I was very hopeful that progesterone was going to work,” says Kurt Denninghoff, MD, Distinguished Professor of Emergency Medicine at the University of Arizona, who served as a hub principal investigator. “The flip side is that we’ve collected biomarkers, we’ve collected data on all the patients at all the sites and we’ve collected information about how they were treated. We have a data set now that the NIH has allowed us to collect by giving us the funding to do this. That is going to change the face of traumatic brain injury treatment and research.”
David Wright, MD, associate professor and vice chair for research in emergency medicine at Emory University School of Medicine, served as lead investigator for the national study, funded by the National Institute of Neurological Disorders and Stroke and organized as part of the NETT (Neurological Emergencies Treatment Trials) network.

Participating patients were 74 percent male, and the average age was 35. The results were not significantly different in men versus women, or in Caucasians, African Americans or Latinos. The most common mechanism of injury was motor vehicle accident.

Of the total 96 patients that were enrolled in Arizona and New Mexico, the following races and ethnicities were represented: Asian (3.13 percent), American Indian/Alaska Native (4.17 percent), Black/African American (5.21 percent), White/Caucasian (86.46 percent), and Hispanic (23.96 percent).

Progesterone, administered by infusion for four days, was generally well-tolerated, with similar rates of adverse events in both progesterone- and placebo-treated groups. Phlebitis (inflammation of a vein) was more common in the progesterone group.

The rationale for testing progesterone grew out of the observation that women tend to respond to treatment and recover better than men after traumatic brain injury. Both men and women naturally produce progesterone, a steroid hormone important for brain development as well as reproductive functions.

Many research teams have found in animal experiments that progesterone can protect brain cells from the toxic environment that emerges after traumatic injury. Two smaller clinical trials of progesterone in traumatic brain injury also gave encouraging results.

Because of a limited time frame (within four hours) for administering progesterone after brain injury, this study was conducted under exception from informed consent (EFIC), following Food and Drug Administration regulations. EFIC is allowed only when testing treatments for life-threatening conditions and when consent from the patient is not possible and treatment efficacy is thought to depend on being administered quickly.

When legally authorized representatives were available, written informed consent was obtained prior to enrollment. For patients enrolled under EFIC, they or their representatives were notified of enrollment as soon as possible and asked for written consent to continue in the study.