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(Stroke. 2008;39:87.)
© 2008 American Heart Association, Inc.

Original Contributions

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)

Harold P. Adams, Jr, MD; Mark B. Effron, MD; James Torner, PhD; Antoni Dávalos, MD, PhD; Judith Frayne, MD; Philip Teal, MD; Jacques Leclerc, MD; Barry Oemar, MD; Lakshmi Padgett, PhD; Elliot S. Barnathan, MD; Werner Hacke, MD for the AbESTT-II Investigators

From the Department of Neurology (H.P.A.), Carver College of Medicine, University of Iowa, Iowa City, USA; Eli Lilly and Company (M.B.E., J.L.), Indianapolis, Ind, USA; Department of Epidemiology (J.T.), College of Public Health, University of Iowa, Iowa City, USA; Department of Neurosciences (A.D.), Hospital Universitari Germans, Badalona, Spain; Stroke Research Unit (J.F.), Monash University, Melbourne, Victoria, Australia; Center for Stroke Research (P.T.), University of British Columbia, Vancouver, BC, Canada; Centocor Research and Development (B.O., L.P., E.S.B.), Malvern, Pa, USA; Department of Neurology (W.H.), University of Heidelberg, Heidelberg, Germany.

Correspondence to Harold P. Adams, Jr, MD, Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA. E-mail harold-adams{at}uiowa.edu, or Werner Hacke, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. E-mail Werner.Hacke@med.uni-heidelberg.de

Background and Purpose— 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, 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.

Key Words: abciximab • acute stroke treatment • hemorrhagic transformation • ischemic stroke

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