Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial

Arthur M. Pancioli, Opeolu Adeoye, Pamela A. Schmit, Jane Khoury, Steven R. Levine, Thomas A. Tomsick, Heidi Sucharew, Claudette E. Brooks, Todd J. Crocco, Laurie Gutmann, Thomas M. Hemmen, Scott E. Kasner, Dawn Kleindorfer, William A. Knight, Sharyl Martini, James S. McKinney, William J. Meurer, Brett C. Meyer, Alexander Schneider, Phillip A. ScottSidney Starkman, Steven Warach, Joseph P. Broderick

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background and Purpose - In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEARER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. Methods - CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. Results - Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). Conclusions - The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen.

Original languageEnglish (US)
Pages (from-to)2381-2387
Number of pages7
JournalStroke
Volume44
Issue number9
DOIs
StatePublished - Sep 2013

Fingerprint

Tissue Plasminogen Activator
Stroke
Safety
Intracranial Hemorrhages
Odds Ratio
Confidence Intervals
National Institutes of Health (U.S.)
eptifibatide
Logistic Models
Outcome Assessment (Health Care)
Incidence

Keywords

  • Clinical trial
  • Eptifibatide
  • Ischemic stroke
  • Tissue plasminogen activator

ASJC Scopus subject areas

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

Cite this

Pancioli, A. M., Adeoye, O., Schmit, P. A., Khoury, J., Levine, S. R., Tomsick, T. A., ... Broderick, J. P. (2013). Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke, 44(9), 2381-2387. https://doi.org/10.1161/STROKEAHA.113.001059

Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. / Pancioli, Arthur M.; Adeoye, Opeolu; Schmit, Pamela A.; Khoury, Jane; Levine, Steven R.; Tomsick, Thomas A.; Sucharew, Heidi; Brooks, Claudette E.; Crocco, Todd J.; Gutmann, Laurie; Hemmen, Thomas M.; Kasner, Scott E.; Kleindorfer, Dawn; Knight, William A.; Martini, Sharyl; McKinney, James S.; Meurer, William J.; Meyer, Brett C.; Schneider, Alexander; Scott, Phillip A.; Starkman, Sidney; Warach, Steven; Broderick, Joseph P.

In: Stroke, Vol. 44, No. 9, 09.2013, p. 2381-2387.

Research output: Contribution to journalArticle

Pancioli, AM, Adeoye, O, Schmit, PA, Khoury, J, Levine, SR, Tomsick, TA, Sucharew, H, Brooks, CE, Crocco, TJ, Gutmann, L, Hemmen, TM, Kasner, SE, Kleindorfer, D, Knight, WA, Martini, S, McKinney, JS, Meurer, WJ, Meyer, BC, Schneider, A, Scott, PA, Starkman, S, Warach, S & Broderick, JP 2013, 'Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial', Stroke, vol. 44, no. 9, pp. 2381-2387. https://doi.org/10.1161/STROKEAHA.113.001059
Pancioli, Arthur M. ; Adeoye, Opeolu ; Schmit, Pamela A. ; Khoury, Jane ; Levine, Steven R. ; Tomsick, Thomas A. ; Sucharew, Heidi ; Brooks, Claudette E. ; Crocco, Todd J. ; Gutmann, Laurie ; Hemmen, Thomas M. ; Kasner, Scott E. ; Kleindorfer, Dawn ; Knight, William A. ; Martini, Sharyl ; McKinney, James S. ; Meurer, William J. ; Meyer, Brett C. ; Schneider, Alexander ; Scott, Phillip A. ; Starkman, Sidney ; Warach, Steven ; Broderick, Joseph P. / Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. In: Stroke. 2013 ; Vol. 44, No. 9. pp. 2381-2387.
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author = "Pancioli, {Arthur M.} and Opeolu Adeoye and Schmit, {Pamela A.} and Jane Khoury and Levine, {Steven R.} and Tomsick, {Thomas A.} and Heidi Sucharew and Brooks, {Claudette E.} and Crocco, {Todd J.} and Laurie Gutmann and Hemmen, {Thomas M.} and Kasner, {Scott E.} and Dawn Kleindorfer and Knight, {William A.} and Sharyl Martini and McKinney, {James S.} and Meurer, {William J.} and Meyer, {Brett C.} and Alexander Schneider and Scott, {Phillip A.} and Sidney Starkman and Steven Warach and Broderick, {Joseph P.}",
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TY - JOUR

T1 - Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial

AU - Pancioli, Arthur M.

AU - Adeoye, Opeolu

AU - Schmit, Pamela A.

AU - Khoury, Jane

AU - Levine, Steven R.

AU - Tomsick, Thomas A.

AU - Sucharew, Heidi

AU - Brooks, Claudette E.

AU - Crocco, Todd J.

AU - Gutmann, Laurie

AU - Hemmen, Thomas M.

AU - Kasner, Scott E.

AU - Kleindorfer, Dawn

AU - Knight, William A.

AU - Martini, Sharyl

AU - McKinney, James S.

AU - Meurer, William J.

AU - Meyer, Brett C.

AU - Schneider, Alexander

AU - Scott, Phillip A.

AU - Starkman, Sidney

AU - Warach, Steven

AU - Broderick, Joseph P.

PY - 2013/9

Y1 - 2013/9

N2 - Background and Purpose - In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEARER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. Methods - CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. Results - Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). Conclusions - The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen.

AB - Background and Purpose - In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEARER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. Methods - CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. Results - Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). Conclusions - The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen.

KW - Clinical trial

KW - Eptifibatide

KW - Ischemic stroke

KW - Tissue plasminogen activator

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