RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED TRIAL OF TIRILAZAD MESYLATE IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE - A COOPERATIVE STUDY IN EUROPE, AUSTRALIA, AND NEW-ZEALAND

Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been show n in experimental models to reduce vasospasm following subarachnoid he morrhage (SAH) and to reduce infarct size from focal cerebral ischemia . To test whether treatment with tirilazad would reduce ischemic sympt oms from vasospasm and improve overall outcome in patients with ruptur ed aneurysms, a prospective randomized, double-blind, vehicle-controll ed trial was conducted at 41 neurosurgical centers in Europe, Australi a, and New Zealand. One thousand twenty-three patients were randomly a ssigned to receive 0.6, 2, or 6 mg/kg per day of intravenously adminis tered tirilazad or a placebo containing the citrate vehicle. All patie nts were also treated with intravenously administered nimodipine. Pati ents 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 wit h 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 w ith tirilazad were predominantly shown in men rather than in women. Th ere were no material differences between the outcomes in the groups tr eated with 0.6 and 2 mg/kg tirilazad per day and the group treated wit h vehicle. Tirilazad was well tolerated at all three dose levels. Thes e 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.