title: Very Early Administration of Progesterone Does Not Improve Neuropsychological Outcomes in Subjects with Moderate to Severe Traumatic Brain Injury.
abstract: A Phase III, double-blind, placebo-controlled trial (ProTECT III) found that administration of progesterone did not reduce mortality or improve functional outcome as measured by the Glasgow Outcome Scale Extended (GOSE) in subjects with moderate to severe traumatic brain injury. We conducted a secondary analysis of neuropsychological outcomes to evaluate whether progesterone is associated with improved recovery of cognitive and motor functioning. ProTECT III was conducted at 49 level I trauma centers in the United States. Adults with moderate to severe TBI were randomized to receive intravenous progesterone or placebo within 4 h of injury for a total of 4 days. At 6 months, subjects underwent evaluation of memory, attention, executive functioning, language, and fine motor coordination/dexterity. Chi-square analysis revealed no significant difference in the proportion of subjects (263/280 progesterone, 283/295 placebo) with Galveston Orientation and Amnesia Test scores ≥75. Analyses of covariance did not reveal significant treatment effects for memory (Buschke immediate recall, p = 0.53; delayed recall, p = 0.94), attention (Trails A speed, p = 0.81 and errors, p = 0.22; Digit Span Forward length, p = 0.66), executive functioning (Trails B speed, p = 0.97 and errors, p = 0.93; Digit Span Backward length, p = 0.60), language (timed phonemic fluency, p = 0.05), and fine motor coordination/dexterity (Grooved Pegboard dominant hand time, p = 0.75 and peg drops, p = 0.59; nondominant hand time, p = 0.74 and peg drops, p = 0.61). Pearson Product Moment Correlations demonstrated significant (p < 0.001) associations between better neuropsychological performance and higher GOSE scores. Similar to the ProTECT III trial's results of the primary outcome, the secondary outcomes do not provide evidence of a neuroprotective effect of progesterone.
authors.affiliation: 1 Department of Neurology, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Felicia C
authors.initials: FC
authors.lastname: Goldstein
authors.affiliation: 2 Department of Psychiatry, University of Michigan , Ann Arbor, Michigan.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Caveney
authors.affiliation: 3 School of Nursing, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Vicki S
authors.initials: VS
authors.lastname: Hertzberg
authors.affiliation: 4 Department of Emergency Medicine, University of Michigan Medical School , Ann Arbor, Michigan.
authors.forename: Robert
authors.initials: R
authors.lastname: Silbergleit
authors.affiliation: 5 Department of Public Health Sciences, Medical University of South Carolina , Charleston, South Carolina.
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Yeatts
authors.affiliation: 5 Department of Public Health Sciences, Medical University of South Carolina , Charleston, South Carolina.
authors.forename: Yuko Y
authors.initials: YY
authors.lastname: Palesch
authors.affiliation: 6 Department of Physical Medicine & Rehabilitation, Baylor College of Medicine , Houston, Texas.
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Levin
authors.affiliation: 7 Department of Emergency Medicine, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000070642:Brain Injuries, Traumatic / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011374:Progesterone
keywords: adult brain injury; clinical trial; cognitive function; head trauma; prospective study