A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). The RANTTAS Investigators.
OBJECTIVE
Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid lipid peroxidation inhibitor, has shown promise as a neuroprotectant in experimental models of focal cerebral ischemia.


METHODS
To test whether early treatment with tirilazad, 6 mg/kg per day for 3 days, 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 measured by the Glasgow Outcome Scale and activities of daily living by the Barthel Index determined 3 months after stroke.


RESULTS
From May 1993 through December 1994, 660 patients were randomized. The trial was prematurely terminated on the advice of an independent monitoring committee after review of outcome data at a preplanned interim analysis. In 556 fully eligible patients (276 tirilazad, 280 vehicle), the odds ratio of a favorable outcome in favor of tirilazad was 0.87 (95% confidence 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 hours after stroke, does not improve overall functional outcome.
D000203:Activities of Daily Living; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007275:Injections, Intravenous; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D011281:Pregnatrienes / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000975:Antioxidants; D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad