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 journalArticlepeer-review

51 Scopus citations

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 1 2013

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial'. Together they form a unique fingerprint.

Cite this