Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas)

Steve Putman, Frances Anderson, M. Rae Morrison, Paul Turtle, Barry T. Passini, Andrew N. Wilner, Fred H. Allen, Robert Adams, Betsy Carl, Carol Bueke, Fenwick T Nichols, David C Hess, Syed Hyder, Gordon Burch, Candy Foley, Don H. Bivins, James T. Wilson, Michael A. Sisk, Donald B. Nolan, William S. EliasGeorge L. Sheppard, Neil F. Crowe, Sandra Massey, Debbie Hurst, David Zontine, Kathryn H. Gustin, E. Clarke Haley, Kathy McClure, Mark Granner, Steven Wolf, Matthews Gwynn, Ray W. Mettetal, E. Clarke Haley, James C. Tomer, Gail Kongable, Sandra Wilkinson, Carolyn Apperson Hansen, Mark C. Wolff, Robert S. Gibson, James D. Bergin, Laura Truskowski, Gene Lightfoot, Angela Lightfoot, Angela Polin, Nina J. Solenski, Judy Stiteler, Gary R. Peters, William J. Bryan

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Background and Purpose Tirilazad mesylate, a 21-amino-steroid, is a potent membrane lipid peroxidation inhibitor and free radical scavenger that has shown promise in animal models of focal cerebral ischemia. Safety in patients with acute ischemic stroke has not yet been established. Methods The study comprised a randomized (three drugs to one vehicle), vehicle-controlled, double-blind, sequential dose-escalation trial at five centers. Treatment was begun within 12 hours of stroke onset and was continued intravenously for 3 days. Results One hundred eleven patients (mean±SD age, 66±13 years; 56% male) were enrolled in three successive dosage tiers: 36 at 0.6 mg/kg per day, 35 at 2.0 mg/kg per day, and 40 at 6.0 mg/kg per day. Median time from stroke onset to treatment was 8.5 (range, 3 to 12) hours and was not significantly different among the groups. Tirilazad was well tolerated at all three doses, except for mild-to-moderate injection site irritation that occurred in both the tirilazad- and vehicle-treated groups. No significant differences in measures of either cardiac or hepatic toxicity were observed in this small sample. Imbalances in baseline medical and Neurological condition made comparisons of outcome difficult. Although no evidence suggestive of tirilazad efficacy was apparent in this study, the trial was not designed to test for differences in outcome. Conclusions These observations suggest that intravenous tirilazad at doses of up to 6.0 mg/kg per day for 3 days is well tolerated in this population of predominantly elderly stroke patients. Larger studies with earlier treatment will be needed to demonstrate efficacy. (Stroke. 1994;25:418-423.).

Original languageEnglish (US)
Pages (from-to)418-423
Number of pages6
JournalStroke
Volume25
Issue number2
DOIs
StatePublished - Feb 1994

Keywords

  • Cerebral infarction
  • Cerebral ischemia
  • Free radicals
  • Lipid peroxidation

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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    Putman, S., Anderson, F., Morrison, M. R., Turtle, P., Passini, B. T., Wilner, A. N., Allen, F. H., Adams, R., Carl, B., Bueke, C., Nichols, F. T., Hess, D. C., Hyder, S., Burch, G., Foley, C., Bivins, D. H., Wilson, J. T., Sisk, M. A., Nolan, D. B., ... Bryan, W. J. (1994). Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas). Stroke, 25(2), 418-423. https://doi.org/10.1161/01.STR.25.2.418