title: Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.
abstract: OBJECTIVE
  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 (CLEAR-ER) 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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00894803.
authors.affiliation: Department of Emergency Medicine, University of Cincinnati Neuroscience Institute, Cincinnati, OH, USA. Arthur.Pancioli@uc.edu
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Pancioli
authors.forename: Opeolu
authors.initials: O
authors.lastname: Adeoye
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Schmit
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Tomsick
authors.forename: Heidi
authors.initials: H
authors.lastname: Sucharew
authors.forename: Claudette E
authors.initials: CE
authors.lastname: Brooks
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Crocco
authors.forename: Laurie
authors.initials: L
authors.lastname: Gutmann
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hemmen
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: William A
authors.initials: WA
authors.lastname: Knight
authors.forename: Sharyl
authors.initials: S
authors.lastname: Martini
authors.forename: James S
authors.initials: JS
authors.lastname: McKinney
authors.forename: William J
authors.initials: WJ
authors.lastname: Meurer
authors.forename: Brett C
authors.initials: BC
authors.lastname: Meyer
authors.forename: Alexander
authors.initials: A
authors.lastname: Schneider
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Scott
authors.forename: Sidney
authors.initials: S
authors.lastname: Starkman
authors.forename: Steven
authors.initials: S
authors.lastname: Warach
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects* / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide
keywords: clinical trial; eptifibatide; ischemic stroke; tissue plasminogen activator