A Clinical Trial of Progesterone for Severe Traumatic Brain Injury
Top Cited Papers
- 25 December 2014
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 371 (26), 2467-2476
- https://doi.org/10.1056/nejmoa1411090
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.)This publication has 25 references indexed in Scilit:
- Progesterone's role in neuroprotection, a review of the evidenceBrain Research, 2013
- Changing patterns in the epidemiology of traumatic brain injuryNature Reviews Neurology, 2013
- Trends in Traumatic Brain Injury in the U.S. and the public health response: 1995–2009Journal of Safety Research, 2012
- Progesterone Receptors: A Key for Neuroprotection in Experimental StrokeEndocrinology, 2012
- Moderate and severe traumatic brain injury in adultsThe Lancet Neurology, 2008
- Classification of Traumatic Brain Injury for Targeted TherapiesJournal of Neurotrauma, 2008
- Neurosteroids reduce inflammation after TBI through CD55 inductionNeuroscience Letters, 2007
- Progesterone Improves Acute Recovery after Traumatic Brain Injury in the Aged RatJournal of Neurotrauma, 2007
- Female sex steroids: effects upon microglial cell activationJournal of Neuroimmunology, 2000
- Head Injury in Man and Experimental Animals: NeuropathologyActa neurochirurgica. Supplement, 1983