ProTECT: Single Center, Phase II (Pilot), Double Blind, 4:1 Randomized, Placebo Controlled Clinical Trial for Progesterone Treatment of Moderate and Severe Blunt TBI

Title: Progesterone Treatment of Blunt Traumatic Brain Injury Principal Investigator(s): Arthur Kellermann, M.D., M.P.H. Institution: Emory University Biostatistician: Vicki Hertzberg, Ph.D. Institution: Emory University Project phase or primary methodology: Phase II pilot, double blind, 4:1 randomized controlled, clinical trial Target disease: Blunt traumatic brain injury Intervention: Intravenous progesterone infused over three days Number of patients to be enrolled: 100 Number of clinical centers: One (Grady Memorial Hospital) Primary Hypothesis: Dose: Intravenous infusion of progesterone at a dose of 0.5 mg/kg/hr produces a steady state of 450 +/- 100 nmol/L in male and female subjects.

Safety: Compared to study subjects who receive placebo, subjects who receive IV progesterone do not have an increased risk of mortality or an increased incidence of adverse effects.

Efficacy: Administering IV progesterone shortly following TBI produces any or all of the following effects, including:

• Reduction of the intracranial pressure therapeutic intensity level (ICP-TIL).
• Decreased duration of coma.
• Decreased inpatient mortality.
• Improved neurological outcome one month post-injury.

Secondary Hypotheses: Benefit: The benefits of IV progesterone for TBI are evident across a range of clinically relevant treatment subgroups, regardless of: