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 Wilner, Fred H. Allen, Robert Adams, Betsy Carl, Carol Bueke, Fenwick Nichols, David Hess, Syed Hyder, Gordon Burch, Candy Foley, Don H. Bivins, James T. Wilson, Michael A. Sisk, Donald B. Nolan, William S. Elias & 28 others George 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

63 Citations (Scopus)

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 - Jan 1 1994

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Stroke
Safety
Free Radical Scavengers
Patient Safety
Membrane Lipids
Brain Ischemia
Therapeutics
Animal Models
Steroids
tirilazad
Injections
Liver
Pharmaceutical Preparations
Population

All Science Journal Classification (ASJC) codes

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

Cite this

Putman, S., Anderson, F., Morrison, M. R., Turtle, P., Passini, B. T., Wilner, A., ... 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

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

In: Stroke, Vol. 25, No. 2, 01.01.1994, p. 418-423.

Research output: Contribution to journalArticle

Putman, S, Anderson, F, Morrison, MR, Turtle, P, Passini, BT, Wilner, A, Allen, FH, Adams, R, Carl, B, Bueke, C, Nichols, F, Hess, D, Hyder, S, Burch, G, Foley, C, Bivins, DH, Wilson, JT, Sisk, MA, Nolan, DB, Elias, WS, Sheppard, GL, Crowe, NF, Massey, S, Hurst, D, Zontine, D, Gustin, KH, Haley, EC, McClure, K, Granner, M, Wolf, S, Gwynn, M, Mettetal, RW, Haley, EC, Tomer, JC, Kongable, G, Wilkinson, S, Apperson Hansen, C, Wolff, MC, Gibson, RS, Bergin, JD, Truskowski, L, Lightfoot, G, Lightfoot, A, Polin, A, Solenski, NJ, Stiteler, J, Peters, GR & Bryan, WJ 1994, 'Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas)', Stroke, vol. 25, no. 2, pp. 418-423. https://doi.org/10.1161/01.STR.25.2.418
Putman S, Anderson F, Morrison MR, Turtle P, Passini BT, Wilner A et al. Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas). Stroke. 1994 Jan 1;25(2):418-423. https://doi.org/10.1161/01.STR.25.2.418
Putman, Steve ; Anderson, Frances ; Morrison, M. Rae ; Turtle, Paul ; Passini, Barry T. ; Wilner, Andrew ; Allen, Fred H. ; Adams, Robert ; Carl, Betsy ; Bueke, Carol ; Nichols, Fenwick ; Hess, David ; Hyder, Syed ; Burch, Gordon ; Foley, Candy ; Bivins, Don H. ; Wilson, James T. ; Sisk, Michael A. ; Nolan, Donald B. ; Elias, William S. ; Sheppard, George L. ; Crowe, Neil F. ; Massey, Sandra ; Hurst, Debbie ; Zontine, David ; Gustin, Kathryn H. ; Haley, E. Clarke ; McClure, Kathy ; Granner, Mark ; Wolf, Steven ; Gwynn, Matthews ; Mettetal, Ray W. ; Haley, E. Clarke ; Tomer, James C. ; Kongable, Gail ; Wilkinson, Sandra ; Apperson Hansen, Carolyn ; Wolff, Mark C. ; Gibson, Robert S. ; Bergin, James D. ; Truskowski, Laura ; Lightfoot, Gene ; Lightfoot, Angela ; Polin, Angela ; Solenski, Nina J. ; Stiteler, Judy ; Peters, Gary R. ; Bryan, William J. / Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas). In: Stroke. 1994 ; Vol. 25, No. 2. pp. 418-423.
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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.).",
author = "Steve Putman and Frances Anderson and Morrison, {M. Rae} and Paul Turtle and Passini, {Barry T.} and Andrew Wilner and Allen, {Fred H.} and Robert Adams and Betsy Carl and Carol Bueke and Fenwick Nichols and David Hess and Syed Hyder and Gordon Burch and Candy Foley and Bivins, {Don H.} and Wilson, {James T.} and Sisk, {Michael A.} and Nolan, {Donald B.} and Elias, {William S.} and Sheppard, {George L.} and Crowe, {Neil F.} and Sandra Massey and Debbie Hurst and David Zontine and Gustin, {Kathryn H.} and Haley, {E. Clarke} and Kathy McClure and Mark Granner and Steven Wolf and Matthews Gwynn and Mettetal, {Ray W.} and Haley, {E. Clarke} and Tomer, {James C.} and Gail Kongable and Sandra Wilkinson and {Apperson Hansen}, Carolyn and Wolff, {Mark C.} and Gibson, {Robert S.} and Bergin, {James D.} and Laura Truskowski and Gene Lightfoot and Angela Lightfoot and Angela Polin and Solenski, {Nina J.} and Judy Stiteler and Peters, {Gary R.} and Bryan, {William J.}",
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T1 - Safety study of tirilazad mesylate in patients with acute ischemic stroke (Stipas)

AU - Putman, Steve

AU - Anderson, Frances

AU - Morrison, M. Rae

AU - Turtle, Paul

AU - Passini, Barry T.

AU - Wilner, Andrew

AU - Allen, Fred H.

AU - Adams, Robert

AU - Carl, Betsy

AU - Bueke, Carol

AU - Nichols, Fenwick

AU - Hess, David

AU - Hyder, Syed

AU - Burch, Gordon

AU - Foley, Candy

AU - Bivins, Don H.

AU - Wilson, James T.

AU - Sisk, Michael A.

AU - Nolan, Donald B.

AU - Elias, William S.

AU - Sheppard, George L.

AU - Crowe, Neil F.

AU - Massey, Sandra

AU - Hurst, Debbie

AU - Zontine, David

AU - Gustin, Kathryn H.

AU - Haley, E. Clarke

AU - McClure, Kathy

AU - Granner, Mark

AU - Wolf, Steven

AU - Gwynn, Matthews

AU - Mettetal, Ray W.

AU - Haley, E. Clarke

AU - Tomer, James C.

AU - Kongable, Gail

AU - Wilkinson, Sandra

AU - Apperson Hansen, Carolyn

AU - Wolff, Mark C.

AU - Gibson, Robert S.

AU - Bergin, James D.

AU - Truskowski, Laura

AU - Lightfoot, Gene

AU - Lightfoot, Angela

AU - Polin, Angela

AU - Solenski, Nina J.

AU - Stiteler, Judy

AU - Peters, Gary R.

AU - Bryan, William J.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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.).

AB - 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.).

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