High-Dose Progesterone To Be Studied in Brain-Injured Patients

On the basis of improved survival in a small pilot study, selected patients with severe traumatic brain injury (TBI) will undergo treatment with natural progesterone in a soon-to-begin, multicenter, phase 3 study throughout the United States. The trial, led by Emory's David Wright, is unusual in that it will forgo the typical FDA requirement of informed consent to allow for the timely administration of therapy.

More than 1000 adults will receive randomized treatment, in a 4-to-1 ratio, of high-dose IV progesterone or placebo over the course of 4 days after emergency presentation. The primary outcome measure is the Extended Glasgow Outcome Scale score at 6 months. Secondary outcome measures, also at 6 months, include mortality, adverse events, and neurologic function. The trial is expected to be completed in 2015.

According to Dr. Wright, as quoted by BBC News, the progesterone dose in the trial will result in a blood level that is about 3 times higher than that found during the third trimester of pregnancy. Preclinical studies suggest that natural, but not synthetic, progesterone is neuroprotective—despite the chemical similarity of the molecules.

Sagittal view of shear stress in head model from sandia.gov.