To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 
21-aminosteroid, in improving the outcome of patients with aneurysmal 
subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective 
randomized, double-blind, vehicle-controlled trial at 54 North American 
neurosurgical centers. Five patients were excluded prior to receiving any study 
drug. Of 897 patients who received at least one dose of study medication, 300 
received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day 
tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered 
intravenously beginning within 48 hours of the SAH and continuing through 10 
days posthemorrhage. All patients were also treated with orally administered 
nimodipine. At 3 months post-SAH, there were no significant differences (p < 
0.025) among the groups with regard to mortality rate, favorable outcome on the 
Glasgow Outcome Scale, or employment status. During the first 14 days after the 
SAH, there were no significant differences among the groups in the incidence or 
severity of clinically symptomatic or angiographically identifiable cerebral 
vasospasm. Mortality data stratified by gender and neurological grade on 
admission (assessed according to a modified World Federation of Neurological 
Surgeons scale) demonstrated that the men with Grades IV to V had a 33% 
mortality rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group 
(p = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad 
was well tolerated at both dose levels. Tirilazad mesylate at dosage levels of 
up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall 
outcome in patients with aneurysmal SAH in this trial. The differences in the 
efficacy of tirilazad in this trial and a previously reported trial in Europe, 
Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per 
day reduced mortality rates and increased good recovery, may be a result of 
differences in admission characteristics of the patients and/or differences in 
management protocols, including the use of anticonvulsant medications.