A clinical trial of progesterone for severe traumatic brain injury

Brett E. Skolnick, Andrew I. Maas, Raj K. Narayan, Roland Gerritsen Van Der Hoop, Thomas MacAllister, John D. Ward, Neta R. Nelson, Nino Stocchetti

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

BACKGROUND 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.

METHODS 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.

RESULTS 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.

CONCLUSIONS 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.

Original languageEnglish
Pages (from-to)2467-2476
Number of pages10
JournalNew England Journal of Medicine
Volume371
Issue number26
DOIs
Publication statusPublished - Dec 25 2014

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Progesterone
Clinical Trials
Placebos
Glasgow Outcome Scale
Randomized Controlled Trials
Safety
Social Adjustment
Phase III Clinical Trials
Glasgow Coma Scale
Wounds and Injuries
Pupil
Traumatic Brain Injury
Consciousness
Animal Models
Odds Ratio
Confidence Intervals
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Skolnick, B. E., Maas, A. I., Narayan, R. K., Van Der Hoop, R. G., MacAllister, T., Ward, J. D., ... Stocchetti, N. (2014). A clinical trial of progesterone for severe traumatic brain injury. New England Journal of Medicine, 371(26), 2467-2476. https://doi.org/10.1056/NEJMoa1411090

A clinical trial of progesterone for severe traumatic brain injury. / Skolnick, Brett E.; Maas, Andrew I.; Narayan, Raj K.; Van Der Hoop, Roland Gerritsen; MacAllister, Thomas; Ward, John D.; Nelson, Neta R.; Stocchetti, Nino.

In: New England Journal of Medicine, Vol. 371, No. 26, 25.12.2014, p. 2467-2476.

Research output: Contribution to journalArticle

Skolnick, BE, Maas, AI, Narayan, RK, Van Der Hoop, RG, MacAllister, T, Ward, JD, Nelson, NR & Stocchetti, N 2014, 'A clinical trial of progesterone for severe traumatic brain injury', New England Journal of Medicine, vol. 371, no. 26, pp. 2467-2476. https://doi.org/10.1056/NEJMoa1411090
Skolnick BE, Maas AI, Narayan RK, Van Der Hoop RG, MacAllister T, Ward JD et al. A clinical trial of progesterone for severe traumatic brain injury. New England Journal of Medicine. 2014 Dec 25;371(26):2467-2476. https://doi.org/10.1056/NEJMoa1411090
Skolnick, Brett E. ; Maas, Andrew I. ; Narayan, Raj K. ; Van Der Hoop, Roland Gerritsen ; MacAllister, Thomas ; Ward, John D. ; Nelson, Neta R. ; Stocchetti, Nino. / A clinical trial of progesterone for severe traumatic brain injury. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 26. pp. 2467-2476.
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