Emergency Administration of Abciximab for Treatment of Patients With Acute Ischemic Stroke: Results of an International Phase III Trial

Abstract

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; Pϭ0.944) 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, Ϸ5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (Pϭ0.002). 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. (Stroke. 2008;39:87-99.)

Potential for the Use of the Solitaire Stent for Recanalization of Middle Cerebral Artery Occlusion without a Susceptibility Vessel Sign

“…31 Because platelet activation is a key step in thromboembolism in the reocclusion of an in situ steno-occlusive lesion, [31][32][33][34] intravenous or intra-arterial glycoprotein IIb/IIIa inhibitors could be effective for preventing reocclusion. 32,34 On the basis of the findings of the Abciximab in Emergency Treatment of Stroke Trial, which showed an increased rate of symptomatic or fatal intracranial hemorrhage, 35 we used intravenous or intra-arterial tirofiban in our study only when no contraindication existed.…”

Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and Data

“…Conversely, the AbESTT II trial, a phase III multicenter randomized double-blind placebo-controlled study evaluating the safety and efficacy of abciximab in acute ischemic stroke treated within 6 hours after stroke onset or within 3 hours of awakening with stroke symptoms, was stopped early due to high rates of sICH or fatal ICH in the abciximabtreated patients (5.5% versus 0.5%, P ϭ .002). 35 The data for the use of GP IIb/IIIa inhibitors in conjunction with IAT are even more scant and are limited to case reports. [36][37][38][39][40][41] Deshmukh et al 38 reported 21 patients with large-vessel occlusion refractory to IAT with rtPA who were treated with IV and/or IA abciximab, eptifibatide, or tirofiban.…”

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“…In stroke patients early data for the use of abciximab had indicated a safe use (Burton 2003). A phase-III-study, however, had to be stopped due to an increased bleeding rate and no sufficient efficacy (Adams et al 2008). For the competitive receptor antagonist tirofiban until now only smaller studies without safety concerns are available, also in combination with rtPA (Junghans et al 2001, Seitz et al 2003) -further studies are pending (SATIS).…”