To the Editor:
In a previous communication in Stroke,1 we reported lack of efficacy of tirilazad mesylate (6 mg/kg per day for 3 days) in patients with acute ischemic stroke treated within 6 hours in North American centers and hypothesized that the lack of benefit may have been secondary to an inadequate dose, especially in females. Studies testing higher doses in both males (12.5 mg/kg on the first day, then 10 mg/kg/d for 2 days) and females (15 mg/kg on the first day, then 12 mg/kg/d) were begun. This letter reports a synopsis of results of the high-dose study in North American (RANTTAS II), which was prematurely stopped by the sponsor when questions regarding safety emerged from a parallel study in Europe (TESS II).
One hundred twenty-six (14% of the planned sample size) patients were enrolled in RANTTAS II within 4 hours of the onset of symptoms. Of these, 111 were fully eligible patients with ischemic stroke: 53 in the tirilazad group, and 58 in the vehicle group. There was an approximate balance in the baseline characteristics of the patients in each treatment group; the median entry NIH Stroke Scale score was 12 in the tirilazad group and 13 in the placebo group. The Table⇓ shows the results of the primary end point measurement, the Barthel Index at 3 months.
The high doses of tirilazad and vehicle were reasonably well tolerated, though the incidence of drug-related infusion site disorders was fairly high in both groups (46% tirilazad, 24% vehicle). No fully eligible patient had premature termination of the study drug because of perceived intolerance of the medication.
To summarize, tirilazad treatment of fully eligible stroke patients was associated with an absolute reduction in mortality of 14% and an increase in the proportion of patients who were independent (Barthel Index score of ≥60) at 3 months. The potential benefits were observed in both men and women. The observed differences were not statistically significant, however, and need to be confirmed in a larger study. No evidence for harm emerged from this experience.
- Copyright © 1998 by American Heart Association