Safety study of tirilazad mesylate in patients with acute ischemic stroke (STIPAS).
Open accessAbstract
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. 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. 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. 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.
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Cites
ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale
JENNETT, B. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92830-5 · Cited by 7,501 · see citing works
Meinert, C. L. (1986) · DigitalGeorgetown (Georgetown University Library) · doi:10.1093/acprof:oso/9780195035681.001.0001 · Cited by 509 · see citing works
Measurements of acute cerebral infarction: lesion size by computed tomography.
Brott, T. G., Marler, J. R., Olinger, C. P., Adams, H. P., Tomsick, T. A., Barsan, W. G., Biller, J., EBERLE, R. W., Hertzberg, V., & Walker, M. (1989) · Stroke · doi:10.1161/01.str.20.7.871 · Cited by 384 · see citing works
Braughler, J. M., Hall, E. D., Jacobsen, E. J., MCCALL, J. M., & Means, E. D. (1989) · Drugs of the Future · doi:10.1358/dof.1989.014.02.101095 · Cited by 124 · see citing works
Fleishaker, J. C., Peters, G. R., & Cathcart, K. S. (1993) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1993.tb03940.x · Cited by 57 · see citing works
The Effect of the 21-Aminosteroid U74006F in a Rabbit Model of Thromboembolic Stroke
Wilson, J. T., Bednar, M. M., McAuliffe, T. L., Raymond, S. J., & Gross, C. E. (1992) · Neurosurgery · doi:10.1097/00006123-199211000-00016 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Medical and Neurological Complications of Ischemic Stroke
Johnston, K. C., Li, J. Y., Lyden, P. D., Hanson, S. K., Feasby, T. E., Adams, R. J., Faught, E., & Haley, E. C. (1998) · Stroke · doi:10.1161/01.str.29.2.447 · Cited by 425 · see citing works
Zhao, H., Sapolsky, R. M., & Steinberg, G. K. (2006) · Molecular Neurobiology · doi:10.1385/mn:34:3:249 · Cited by 274 · see citing works
Statistical Analysis of the Primary Outcome in Acute Stroke Trials
Bath, P. M. W., Lees, K. R., Schellinger, P. D., Altman, H., Bland, M., Hogg, C., Howard, G., & Saver, J. L. (2012) · Stroke · doi:10.1161/strokeaha.111.641456 · Cited by 266 · see citing works
Clinical trials for cytoprotection in stroke
Labiche, L. A., & Grotta, J. C. (2004) · Neurotherapeutics · doi:10.1602/neurorx.1.1.46 · Cited by 122 · see citing works
An Overview of Acute Stroke Therapy: Past, Present, and Future
Fisher, M., & Schaebitz, W. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.21.3196 · Cited by 112 · see citing works
Mechanisms that Result in Damage During and Following Cerebral Ischemia
Juurlink, B. H. J., & Sweeney, M. I. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00001-2 · Cited by 101 · see citing works
Grupke, S. L., Hall, J., Dobbs, M., Bix, G. J., & Fraser, J. F. (2014) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2014.11.013 · Cited by 99 · see citing works
Zausinger, S., Westermaier, T., Plesnila, N., Steiger, H., & Schmid-Elsaesser, R. (2003) · Stroke · doi:10.1161/01.str.0000070841.31224.29 · Cited by 73 · see citing works
Tirilazad mesylate in acute ischemic stroke - A systematic review
Bath, P., Blecic, S. A., Bogousslavsky, J., Boysen, G., Davis, S. M., Díez‐Tejedor, E., Ferro, J. M., Gommans, J., Hacke, W., Indredavik, B., et al. (2000) · Stroke · Cited by 69 · see citing works
Trends and Future Developments in the Pharmacological Treatment of Acute Ischaemic Stroke
del Zoppo, G. J., Wagner, S., & Tagaya, M. (1997) · Drugs · doi:10.2165/00003495-199754010-00002 · Cited by 66 · see citing works
Clark, W. M., Hazel, J., & Coull, B. M. (1995) · Drugs · doi:10.2165/00003495-199550060-00005 · Cited by 64 · see citing works
Should Stroke Trials Adjust Functional Outcome for Baseline Prognostic Factors?
The Optimising the Analysis of Stroke Trials (OAST) Collaboration (2009) · Stroke · doi:10.1161/strokeaha.108.519207 · Cited by 64 · see citing works
Chtita, S., Belhassan, A., Aouidate, A., Belaıdı, S., Bouachrıne, M., & Lakhlifi, T. (2020) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207323999200730205447 · Cited by 62 · see citing works
Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials
Uchino, K., Billheimer, D. D., & Cramer, S. C. (2001) · Stroke · doi:10.1161/01.str.32.4.909 · Cited by 60 · see citing works
Tirilazad for acute ischaemic stroke
The Tirilazad International Steering Committee (2001) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002087 · Cited by 59 · see citing works
Neuroprotection as Initial Therapy in Acute Stroke
Cantú, C., Villarreal, J., Soto‐Hernández, J. L., Barinagarrementería, F., Schoser, B. G. H., Becker, V., Eckert, B., Zeumer, H., & Thie, A. (1998) · Cerebrovascular Diseases · doi:10.1159/000015817 · Cited by 59 · see citing works
Review : Neuroprotection in Brain Ischemia: An Update (Part II
Ginsberg, M. D. (1995) · The Neuroscientist · doi:10.1177/107385849500100307 · Cited by 55 · see citing works
Grasbon-Frodl, E. M., Nakao, N., & Brundin, P. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(96)00001-9 · Cited by 54 · see citing works
Limiting Neurological Damage After Stroke
Read, S. J., Hirano, T., Davis, S. M., & Donnan, G. A. (1999) · Drugs & Aging · doi:10.2165/00002512-199914010-00002 · Cited by 43 · see citing works
Recently Developed Neuroprotective Therapies for Acute Stroke
Dorman, P. J., Counsell, C. E., & Sandercock, P. A. (1996) · CNS Drugs · doi:10.2165/00023210-199605060-00005 · Cited by 39 · see citing works
Tirilazad Mesylate Improves Survival of Rat and Human Embryonic Mesencephalic Neuronsin Vitro
Othberg, A. I., Keep, M. F., Brundin, P., & Lindvall, O. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6594 · Cited by 38 · see citing works
Synthetic and semi-synthetic antioxidants in medicine and food industry: a review
Tauchen, J., Huml, L., Jurášek, M., Regenstein, J. M., & Özoğul, F. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1599816 · Cited by 31 · see citing works
Takizawa, S., Izuhara, Y., Kitao, Y., Hori, O., Ogawa, S., Morita, Y., Takagi, S., de Strihou, C. V. Y., & Miyata, T. (2007) · Brain Research · doi:10.1016/j.brainres.2007.07.006 · Cited by 31 · see citing works
A Method to Determine Stroke Trial Success Using Multidimensional Pooled Control Functions
Mandava, P., & Kent, T. A. (2009) · Stroke · doi:10.1161/strokeaha.108.532820 · Cited by 30 · see citing works
Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review
Mulder, I. A., VanBavel, E., de Vries, H. E., & Coutinho, J. M. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00280-1 · Cited by 26 · see citing works
Dietrich, W. D. (1998) · International review of neurobiology · doi:10.1016/s0074-7742(08)60608-x · Cited by 26 · see citing works
Combination Therapy with Neuroprotectants and Thrombolytics in Acute Ischaemic Stroke
Steiner, T., & Hacke, W. (1998) · European Neurology · doi:10.1159/000007947 · Cited by 26 · see citing works
Chapter 15 A Review of Earlier Clinical Studies on Neuroprotective Agents and Current Approaches
Wahlgren, N. G. (1996) · International review of neurobiology · doi:10.1016/s0074-7742(08)60727-8 · Cited by 23 · see citing works
Pharmacological approaches to the treatment and prevention of aphasia
Shisler, R. J., Baylis, G. C., & Frank, E. M. (2000) · Aphasiology · doi:10.1080/02687030050205705 · Cited by 21 · see citing works
Gender does not affect the degree of induction of tirilazad clearance by phenobarbital
Fleishaker, J. C., Pearson, L. K., & Peters, G. R. (1996) · European Journal of Clinical Pharmacology · doi:10.1007/s002280050082 · Cited by 20 · see citing works
CNS Pharmacology and Current Research
Clark, W. M., Hazel, J., & Coull, B. M. (1995) · Cited by 15 · see citing works
Neuroprotection in acute ischaemic stroke. II: Clinical potential
Davis, M., & Barer, D. H. (1999) · Vascular Medicine · doi:10.1177/1358836x9900400306 · Cited by 13 · see citing works
Fleishaker, J. C., & Peters, G. R. (1996) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1996.tb04254.x · Cited by 11 · see citing works
Fleishaker, J. C., Straw, R. N., & Cross, C. J. (1997) · Journal of Pharmaceutical Sciences · doi:10.1021/js960410e · Cited by 10 · see citing works
The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke
Bath, P. M., Appleton, J. P., & England, T. J. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4107 · Cited by 8 · see citing works
Current and Future Options for the Prevention and Treatment of Stroke
Besson, G., & Bogousslavsky, J. (1995) · CNS Drugs · doi:10.2165/00023210-199503050-00004 · Cited by 8 · see citing works
Pharmacologic Modification of Acute Cerebral Ischemia
Gonzales, N. R., & Grotta, J. C. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-5478-8.10053-3 · Cited by 8 · see citing works
Fleishaker, J. C., Pearson, P. G., Wienkers, L. C., Pearson, L. K., Moore, T. A., & Peters, G. R. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37832-2 · Cited by 7 · see citing works
Lazaroids inhibit proliferation of cultured human astrocytoma cells
Arora, P., Lee, Y. S., Origitano, T. C. O., & Wurster, R. D. (1996) · Journal of Neuro-Oncology · doi:10.1007/bf00182137 · Cited by 5 · see citing works
Tissue rescue therapy for acute ischaemic stroke
Davis, S. M. (1995) · Journal of Clinical Neuroscience · doi:10.1016/0967-5868(95)90023-3 · Cited by 5 · see citing works
Recent advances in cardiovascular pharmacology
Frishman, W. H. (2000) · Current Problems in Cardiology · doi:10.1016/s0146-2806(00)70011-9 · Cited by 4 · see citing works
Pharmacological Advances in Cerebrovascular Protection
Yenari, M. A., & Steinberg, G. K. (1998) · Springer eBooks · doi:10.1007/978-1-4613-9350-4_10 · Cited by 4 · see citing works
Pharmacologic Modification of Acute Cerebral Ischemia
Labiche, L. A., & Grotta, J. C. (2004) · Elsevier eBooks · doi:10.1016/b0-44-306600-0/50061-4 · Cited by 4 · see citing works
Translati onal challenges of neuroprotection strategy in ischemic stroke
Budinčević, H., Bielen, I., & Csiba, L. (2011) · Translational Neuroscience · doi:10.2478/s13380-011-0041-2 · Cited by 3 · see citing works
Drug Therapy of Neurovascular Disease
Weinberger, J. M., Frishman, W. H., & Terashita, D. M. (2003) · Cardiology in Review · doi:10.1097/01.crd.0000053459.09918.92 · Cited by 3 · see citing works
Brain protection during neurosurgery: an update from the anaesthetist's perspective
Leslie, K., & Solly, M. F. (1995) · Journal of Clinical Neuroscience · doi:10.1016/0967-5868(95)90046-2 · Cited by 3 · see citing works
Davis, S. M., & Donnan, G. A. (1996) · Australian and New Zealand Journal of Medicine · doi:10.1111/j.1445-5994.1996.tb02900.x · Cited by 2 · see citing works
Should data monitoring committees assess efficacy when considering safety in trials in acute stroke?
Bath, P. M., Gray, L. J., & Wahlgren, N. G. (2007) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2007.01471.x · Cited by 2 · see citing works
Neurocritical Care of Intracranial Brain Tumor Surgery: An Overview
Moscote‐Salazar, L. R., Narvaez‐Rojas, A. R., Mo-Carrascal, J., Maraby, J., Satyarthee, G., Hoz, S. S., & Joaquim, A. (2018) · MAMC Journal of Medical Sciences · doi:10.4103/mamcjms.mamcjms_79_17 · Cited by 2 · see citing works
The Stroke Pharmacopeia: Promising Experimental Therapies
Gengo, F. M. (1998) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1998.tb03887.x · Cited by 2 · see citing works
An Overview of Cytoprotective Therapy for Acute Ischemic Stroke
Fisher, M. (1995) · Elsevier eBooks · doi:10.1016/b978-0-7506-9603-6.50038-0 · Cited by 2 · see citing works
The Stroke Therapy Research Boom: Implications for the Hospital Formulary
Bender, N. K. (1998) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1998.tb03888.x · Cited by 1 · see citing works
Naradzay, J. F. X., & Gaasch, W. R. (1996) · Emergency Medicine Clinics of North America · doi:10.1016/s0733-8627(05)70245-5 · Cited by 1 · see citing works
Drugs in Development: New Agents, New Classes, New Indications
Frishman, W. H., Cheng-Lai, A., & Chen, J. (2000) · doi:10.1007/978-1-4615-6767-7_15
Glutamate Receptor Antagonists and the Treatment of Neurological Disorders
Farooqui, A. A., Ong, W., & Horrocks, L. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-73023-3_10
Gusev, E. I., & Skvortsova, V. I. (2003) · Springer eBooks · doi:10.1007/978-1-4419-9248-2_16
Isaac, L. (1997) · Surgical Neurology · doi:10.1016/s0090-3019(97)81987-8
von Bruchhausen, F., Ebel, S., Hackenthal, E., Holzgrabe, U., Albinus, M., Amschler, G., Angerer, E. V., Arras‐Reiter, C., Bauer, A., Bauer, P., et al. (1999) · Springer eBooks · doi:10.1007/978-3-642-58388-9_9
Pharmacotherapy and Economics of Stroke
(1998) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1998.tb03889.x
Arterial Drug Delivery in the Future: Addressing Complex Problems as Acute Ischemic Stroke
Joshi, S., & Ramos, A. D. (2025) · Springer eBooks · doi:10.1007/978-3-031-80173-0_23
- Venue
- Stroke
- Published
- 1994-02
- Volume
- 25
- Issue
- 2
- Pages
- 418-423
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2410266684
- Cited by
- 61
- References
- 6
- Citations by year
- 2025: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2014: 1 · 2012: 1
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- tirilazad mesylate, acute ischemic stroke, drug safety, tolerability, dose escalation, lipid peroxidation inhibition, radical scavengers, intravenous administration, cardiotoxicity, hepatotoxicity, elderly patients
- MeSH terms
- Adult, Aged, Aged, 80 and over, Brain Ischemia, Cerebrovascular Disorders, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Infusions, Intravenous, Lipid Peroxides, Male, Middle Aged, Pregnatrienes, Time Factors, Free Radical Scavengers, Treatment Outcome
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