Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been shown in 
experimental models to reduce vasospasm following subarachnoid hemorrhage (SAH) 
and to reduce infarct size from focal cerebral ischemia. To test whether 
treatment with tirilazad would reduce ischemic symptoms from vasospasm and 
improve overall outcome in patients with ruptured aneurysms, a prospective 
randomized, double-blind, vehicle-controlled trial was conducted at 41 
neurosurgical centers in Europe, Australia, and New Zealand. One thousand 
twenty-three patients were randomly assigned to receive 0.6, 2, or 6 mg/kg per 
day of intravenously administered tirilazad or a placebo containing the citrate 
vehicle. All patients were also treated with intravenously administered 
nimodipine. Patients receiving 6 mg/kg per day of tirilazad had reduced 
mortality (p = 0.01) and a greater frequency of good recovery on the Glasgow 
Outcome Scale 3 months after SAH (p = 0.01) than similar patients treated with 
vehicle. There was a reduction in symptomatic vasospasm in the group that 
received 6 mg/kg per day tirilazad; however, the difference was not 
statistically significant (p = 0.048). The benefits of treatment with tirilazad 
were predominantly shown in men rather than in women. There were no material 
differences between the outcomes in the groups treated with 0.6 and 2 mg/kg 
tirilazad per day and the group treated with vehicle. Tirilazad was well 
tolerated at all three dose levels. These observations suggest that tirilazad 
mesylate, at a dosage of 6 mg/kg per day, is safe and improves overall outcome 
in patients (especially in men) who have experienced an aneurysmal SAH.