title: Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II).
abstract: OBJECTIVE
  A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset.
  
  
  METHODS
  An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke.
  
  
  RESULTS
  The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221; P=0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximately 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (P=0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo).
  
  
  CONCLUSIONS
  This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA. harold-adams@uiowa.edu
authors.forename: Harold P
authors.initials: HP
authors.lastname: Adams
authors.forename: Mark B
authors.initials: MB
authors.lastname: Effron
authors.forename: James
authors.initials: J
authors.lastname: Torner
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: Judith
authors.initials: J
authors.lastname: Frayne
authors.forename: Philip
authors.initials: P
authors.lastname: Teal
authors.forename: Jacques
authors.initials: J
authors.lastname: Leclerc
authors.forename: Barry
authors.initials: B
authors.lastname: Oemar
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Padgett
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
mesh_terms: D000077284:Abciximab; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D004311:Double-Blind Method; D004638:Emergency Treatment / Q000379:methods*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014851:Wakefulness / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D000077284:Abciximab