title: A matched comparison of eptifibatide plus rt-PA versus rt-PA alone in acute ischemic stroke.
abstract: BACKGROUND
  The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that intravenous rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of symptomatic intracranial hemorrhage (sICH) and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the National Institute of Neurological Disorders and Stroke (NINDS) trial.
  
  
  METHODS
  CLEAR-ER was a multicenter, double-blind, randomized study; rt-PA-eligible AIS patients were randomized to .6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard rt-PA (.9 mg/kg). For this analysis, we matched 1:1 CLEAR-ER combination therapy patients with rt-PA arm NINDS trial patients. Patients were matched by age, gender, race, baseline modified Rankin Scale score, baseline National Institutes of Health Stroke Scale (NIHSS) score, and stroke onset to rt-PA time.
  
  
  RESULTS
  Fifty-four matches were made. One (1.8%) sICH occurred in each group (odds ratio [OR] 1.00, 95% confidence interval [CI] .01-78.50). At 90 days, 51.8% of the CLEAR-ER group had good outcomes versus 46.3% in the NINDS rt-PA group (OR 1.30, 95% CI .57-2.96). For subjects with baseline NIHSS score > 12 (CLEAR-ER median NIHSS score), 38.5% of the CLEAR-ER group had good outcomes versus 23.1% in the NINDS group (OR 2.33, 95% CI .60-9.02).
  
  
  CONCLUSIONS
  The safety and direction of effect of eptifibatide plus rt-PA were confirmed. A phase III trial is needed to determine the efficacy of eptifibatide plus rt-PA for improving long-term outcomes after AIS.
authors.affiliation: University of Cincinnati Neuroscience Institute, Cincinnati, Ohio; Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio. Electronic address: opeolu.adeoye@uc.edu.
authors.forename: Opeolu
authors.initials: O
authors.lastname: Adeoye
authors.affiliation: University of Cincinnati Neuroscience Institute, Cincinnati, Ohio; Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio.
authors.forename: William A
authors.initials: WA
authors.lastname: Knight
authors.affiliation: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.affiliation: University of Cincinnati Neuroscience Institute, Cincinnati, Ohio; Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Schmit
authors.affiliation: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Heidi
authors.initials: H
authors.lastname: Sucharew
authors.affiliation: University of Cincinnati Neuroscience Institute, Cincinnati, Ohio; Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: University of Cincinnati Neuroscience Institute, Cincinnati, Ohio; Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Pancioli
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy*; D004185:Disability Evaluation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide
keywords: Ischemic stroke; clinical trial; eptifibatide; tissue plasminogen activator