This Article Order Full text via Infotrieve Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation

Stroke, Vol 25, 418-423, Copyright © 1994 by American Heart Association

ARTICLES

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

Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.

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.

This article has been cited by other articles:

				P. Mandava and T. A. Kent A Method to Determine Stroke Trial Success Using Multidimensional Pooled Control Functions Stroke, May 1, 2009; 40(5): 1803 - 1810. [Abstract] [Full Text] [PDF]

				The Optimising the Analysis of Stroke Trials (OAST Should Stroke Trials Adjust Functional Outcome for Baseline Prognostic Factors? Stroke, March 1, 2009; 40(3): 888 - 894. [Abstract] [Full Text] [PDF]

				The Optimising Analysis of Stroke Trials (OAST) Co Can We Improve the Statistical Analysis of Stroke Trials?: Statistical Reanalysis of Functional Outcomes in Stroke Trials * OAST Supplemental Appendix I: Statistical Tests Compared (see Table I) * OAST Supplemental Appendix II: Supplementary Analyses * OAST Supplemental Appendix III: Trial Data (see Tables II and III) * OAST Supplemental Appendix IV: Results (see Table IV) Stroke, June 1, 2007; 38(6): 1911 - 1915. [Abstract] [Full Text] [PDF]

				S. Zausinger, T. Westermaier, N. Plesnila, H.-J. Steiger, and R. Schmid-Elsaesser Neuroprotection in Transient Focal Cerebral Ischemia by Combination Drug Therapy and Mild Hypothermia: Comparison With Customary Therapeutic Regimen Stroke, June 1, 2003; 34(6): 1526 - 1532. [Abstract] [Full Text] [PDF]

				K. Uchino, D. Billheimer, and S. C. Cramer Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials Stroke, April 1, 2001; 32(4): 909 - 916. [Abstract] [Full Text] [PDF]

				M. Fisher and W. Schaebitz An Overview of Acute Stroke Therapy: Past, Present, and Future Arch Intern Med, November 27, 2000; 160(21): 3196 - 3206. [Full Text] [PDF]

				Tirilazad Mesylate in Acute Ischemic Stroke : A Systematic Review Stroke, September 1, 2000; 31(9): 2257 - 2265. [Abstract] [Full Text] [PDF]

				M. Davis and D. Barer Neuroprotection in acute ischaemic stroke. II: Clinical potential Vascular Medicine, August 1, 1999; 4(3): 149 - 163. [Abstract] [PDF]

				J. C. Fleishaker, P. G. Pearson, L. C. Wienkers, L. K. Pearson, T. A. Moore, and G. R. Peters Biotransformation of Tirilazad in Human: 4. Effect of Finasteride on Tirilazad Clearance and Reduced Metabolite Formation J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 591 - 597. [Abstract] [Full Text]

				A Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS) Stroke, September 1, 1996; 27(9): 1453 - 1458. [Abstract] [Full Text]

				M. D. Ginsberg Review : Neuroprotection in Brain Ischemia: An Update (Part II Neuroscientist, May 1, 1995; 1(3): 164 - 175. [Abstract] [PDF]