AbESTT-II
(2008)Objective
To determine whether early intravenous administration of abciximab within 5 hours of acute ischemic stroke onset would improve functional outcomes at 3 months, and to evaluate its safety in terms of intracranial hemorrhage.
Study Summary
• Abciximab significantly increased symptomatic or fatal intracranial hemorrhage within 5 days: 5.5% vs 0.5% in the primary cohort (P=0.002)
• Wake-up stroke patients treated with abciximab had hemorrhage rates of 13.6% vs 5% for placebo
• Trial terminated early after 808 of 1800 planned patients due to unfavorable benefit-risk profile; no benefit demonstrated in any cohort
Intervention
Intravenous abciximab (0.25 mg/kg bolus followed by 12-hour infusion at 0.125 μg/kg per minute) vs identically appearing placebo, administered within 5 hours of stroke onset
Inclusion Criteria
Age >18 years; acute ischemic stroke with baseline NIHSS 4–22; treatable within 5 hours of onset (primary cohort) or 5–6 hours after onset / within 3 hours of awakening with stroke signs (companion cohort)
Study Design
Arms: Abciximab 0.25 mg/kg bolus + 0.125 μg/kg/min 12-hr infusion (n=221, primary cohort) vs Placebo (n=218, primary cohort); 808 patients total enrolled across all cohorts
Patients per Arm: Primary cohort: Abciximab n=221, Placebo n=218; Total enrolled across all cohorts: 808
Outcome
• Primary safety: symptomatic or fatal ICH within 5 days 5.5% abciximab vs 0.5% placebo (P=0.002) — significantly higher with abciximab
• Wake-up cohort ICH rate: 13.6% abciximab vs 5% placebo; no efficacy benefit in companion or wake-up cohorts
• Trial halted early by independent safety monitoring board for unfavorable benefit-risk profile
Bottom Line
Abciximab should not be used for acute ischemic stroke treatment; it confers no functional benefit and significantly increases the risk of symptomatic or fatal intracranial hemorrhage across all time windows and patient cohorts studied.
Major Points
- Trial terminated prematurely after 808 of 1800 planned patients were enrolled due to an unfavorable benefit-risk profile identified by the independent safety and efficacy monitoring committee
- No improvement in favorable 3-month outcomes in the primary cohort: 32% (71/221) abciximab vs 33% (72/218) placebo (P=0.944); mRS distributions were similar between groups
- Abciximab significantly increased symptomatic or fatal intracranial hemorrhage within 5 days in the primary cohort: 5.5% vs 0.5% for placebo (P=0.002)
- No efficacy benefit demonstrated in the companion cohort (5–6 hours after onset) or wake-up stroke cohort
- Wake-up stroke patients treated with abciximab had particularly high hemorrhage rates (13.6% vs 5% for placebo), though the cohort was small
- Abciximab cannot be recommended for acute ischemic stroke treatment regardless of time window or clinical subgroup
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled phase 3 trial
- Randomization
- Yes
- Blinding
- Double-blind; identically appearing placebo; central CT core laboratory with blinded independent neuroradiologists; blinded Clinical Endpoint Committee
- Sample Size
- 808
- Follow-up
- 3 months (90–120 days); adverse events collected through 3 months; deaths recorded through 120 days
- Centers
- 112
- Countries
- USA, Germany, Spain, Australia, Canada
Primary Outcome
Definition: Proportion of modified Rankin Scale (mRS) responders at 3 months, dichotomized based on baseline NIHSS severity: mRS 0 for NIHSS 4–7; mRS 0–1 for NIHSS 8–14; mRS 0–2 for NIHSS 15–22
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 33% (72/218) | 32% (71/221) | - | 0.944 |
Limitations & Criticisms
- Trial terminated prematurely after enrolling only 45% of the planned 1800 patients (808 enrolled), substantially limiting statistical power for secondary and subgroup analyses
- The companion and wake-up cohorts were small, rendering conclusions about those populations preliminary; the 13.6% hemorrhage rate in the wake-up cohort is based on few patients
- Sponsors (Eli Lilly and Centocor) participated in trial design and conduct, though blinding of the Executive Committee was maintained and an independent monitoring committee oversaw safety decisions
Citation
Adams HP Jr, et al. Stroke. 2008;39:87-99.