A RANDOMIZED TRIAL OF TIRILAZAD MESYLATE IN PATIENTS WITH ACUTE STROKE (RANTTAS)

Background and Purpose Tirilazad mesylate, a nonglucocorticoid 21-amin osteroid lipid peroxidation inhibitor, has shown promise as a neuropro tectant in experimental models of focal cerebral ischemia. Methods To test whether early treatment with tirilazad, 6 mg/kg per day for 3 day s, would improve functional outcome after acute human stroke, 27 North American centers conducted a prospective, randomized, double-blinded, vehicle-controlled trial in patients with acute stroke treated within 6 hours of onset. The primary outcome measures were disability as mea sured by the Glasgow Outcome Scale and activities of daily living by t he Barthel Index determined 3 months after stroke. Results From May 19 93 through December 1994, 660 patients were randomized. The trial was prematurely terminated on the advice of an independent monitoring comm ittee after review of outcome data at a preplanned interim analysis. I n 556 fully eligible patients (276 tirilazad, 280 vehicle), the odds r atio of a favorable outcome in favor of tirilazad was 0.87 (95% confid ence interval [CI], 0.60 to 1.25) for the Glasgow Outcome Scale and 0. 87 (95% CI, 0.60 to 1.25) for the Barthel Index, after adjustment for imbalances between the groups in preexisting disability, prior stroke, and diabetes. Conclusions These observations suggest that tirilazad, 6 mg/kg per day for 3 days administered beginning at a median of 4.3 h ours after stroke, does not improve overall functional outcome.