Very early administration of progesterone for acute traumatic brain injury

David W. Wright, Sharon D. Yeatts, Robert Silbergleit, Yuko Y. Palesch, Vicki S. Hertzberg, Michael Frankel, Felicia C. Goldstein, Angela F. Caveney, Harriet Howlett-Smith, Erin M. Bengelink, Geoffrey T. Manley, Lisa H. Merck, L. Scott Janis, William G. Barsan, David W. Wright, Michael Frankel, Lisa H. Merck, Tamara R. Espinoza, Jeffrey P. Salomone, Sanjay S. DhallPatricia A. Hudgins, Jason W. Allen, Felicia Goldstein, Vicki Hertzberg, Susan D. Rogers, Anna Marie Calcaterra, Harriet Howlett-Smith, Bethany Lane, Michael P. Lunney, N. Renee Cook, Alex Hall, Andy Hall, Andrea McDougal, Anuradha Subramanian, Gustavo Pradilla, Donald G. Stein, Robert Silbergleit, William G. Barsan, Arthur Pancioli, Daniel Lowenstein, William J. Meurer, Lewis B. Morgenstern, Valerie Stevenson, Erin Bengelink, Deneil Harney, Andrace De Yampert, Samkeliso Mawocha, Joy Pinkerton, Angela Caveney, Eric D. Irwin, for the NETT Investigators

Research output: Contribution to journalArticlepeer-review

304 Scopus citations

Abstract

BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI.

Original languageEnglish (US)
Pages (from-to)2457-2466
Number of pages10
JournalNew England Journal of Medicine
Volume371
Issue number26
DOIs
StatePublished - Dec 25 2014

Fingerprint Dive into the research topics of 'Very early administration of progesterone for acute traumatic brain injury'. Together they form a unique fingerprint.

Cite this