Objective: To evaluate outcome of patients with severe closed head injury treated with pegorgotein, a scavenger of oxygen-derived free radicals.
Design: Randomized, parallel, placebo-controlled, third-party-blind, multicenter trial, with a blinded, multicenter follow-up protocol.
Setting: Twenty-nine centers in the United States.
Patients: A total of 463 patients with severe closed head injury and a Glasgow Coma Scale score of 8 or less after resuscitation and stabilization.
Interventions: Patients received a single intravenous dose of placebo, 10 000 U/kg of pegorgotein, or 20 000 U/kg of pegorgotein within 8 hours after injury.
Outcome measures: The primary endpoint was the Glasgow Outcome Scale (GOS) score at 3 months after brain injury with GOS data trichotomized into good, fair, or poor outcome. Secondary efficacy endpoints included the Disability Rating Scale (DRS) and mortality. A secondary analysis was performed using GOS scores dichotomized into favorable and unfavorable outcomes. In a follow-up protocol at 6 months, GOS and DRS scores were again determined.
Results: Of 463 patients randomized, 162 received placebo; 149, pegorgotein 10 000 U/kg; and 152, pegorgotein 20 000 U/kg. Treatment groups were comparable with respect to demographic characteristics, mechanism of injury, and time to treatment. Pegorgotein was well tolerated at both dose levels. At month 3, the trichotomized analysis found no significant statistical difference in neurologic outcome between the pegorgotein and the placebo groups. Although differences were not statistically significant, there were more favorable outcomes and no increase in the number of deaths or vegetative states among the patients given pegorgotein, more subjects had good or favorable outcomes with the 10 000-U/kg dose than with the 20 000-U/kg dose or placebo, and less disability was observed with the 10 000-U/kg dose than with either the 20 000-U/kg dose or placebo. No differences in mortality rate or cause of death were found between the 10 000-U/kg and placebo groups at either month 3 or month 6. The only statistically significant difference between the groups was a decreased incidence of adult respiratory distress syndrome in the 10 000-U/kg group as compared with the placebo group (P<.015).
Conclusions: In this clinical trial of 463 patients with severe head injury, no statistically significant difference in neurologic outcome or mortality was observed between patients treated with pegorgotein and those receiving placebo.