SAFETY STUDY OF TIRILAZAD MESYLATE IN PATIENTS WITH ACUTE ISCHEMIC STROKE (STIPAS)

Background and Purpose Tirilazad mesylate, a 21-aminosteroid, is a pot ent membrane lipid peroxidation inhibitor and free radical scavenger t hat has shown promise in animal models of focal cerebral ischemia. Saf ety in patients with acute ischemic stroke has not yet been establishe d. Methods The study comprised a randomized (three drugs to one vehicl e), vehicle-controlled, double-blind, sequential dose-escalation trial at five centers. Treatment was begun within 12 hours of stroke onset and was continued intravenously for 3 days. Results One hundred eleven patients (mean+/-SD age, 66+/-13 years; 56% male) were enrolled in th ree successive dosage tiers: 36 at 0.6 mg/kg per day, 35 at 2.0 mg/kg per day, and 40 at 6.0 mg/kg per day. Median time from stroke onset to treatment was 8.5 (range, 3 to 12) hours and was not significantly di fferent among the groups. Tirilazad was well tolerated at all three do ses, except for mild-to-moderate injection site irritation that occurr ed in both the tirilazad- and vehicle-treated groups. No significant d ifferences in measures of either cardiac or hepatic toxicity were obse rved in this small sample. Imbalances in baseline medical and neurolog ical condition made comparisons of outcome difficult. Although no evid ence suggestive of tirilazad efficacy was apparent in this study, the trial was not designed to test for differences in outcome. Conclusions These observations suggest that intravenous tirilazad at doses of up to 6.0 mg/kg per day for 3 days is well tolerated in this population o f predominantly elderly stroke patients. Larger studies with earlier t reatment will be needed to demonstrate efficacy.