A clinical trial of progesterone for severe traumatic brain injury.

The New England journal of medicine (2014-12-11)
Brett E Skolnick, Andrew I Maas, Raj K Narayan, Roland Gerritsen van der Hoop, Thomas MacAllister, John D Ward, Neta R Nelson, Nino Stocchetti
ABSTRACT

Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clinical trial. We conducted a multinational placebo-controlled trial, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, ≤8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury. Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064.).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Progesterone, ≥99%
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Supelco
Progesterone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Supelco
Progesterone solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Progesterone, meets USP testing specifications
Supelco
Progesterone, VETRANAL®, analytical standard
Progesterone for system suitability, European Pharmacopoeia (EP) Reference Standard
Progesterone for peak identification, European Pharmacopoeia (EP) Reference Standard
Progesterone, European Pharmacopoeia (EP) Reference Standard
USP
Progesterone, United States Pharmacopeia (USP) Reference Standard