Abciximab Emergent Stroke Treatment Trial - AbESTT
The goal of the trial was to evaluate the safety and efficacy of treatment with abciximab compared with placebo among patients with acute ischemic stroke.
Patients Screened: 5342
Patients Enrolled: 400
Mean Follow Up: 3 months
Mean Patient Age: Mean age 67 years
Age > 18 years with acute ischemic stroke that could be treated within 6 hours of onset of symptoms and baseline NIHSS score 4 to <23.
Disabled prior to stroke; received rtPA in prior 3 hours for stroke; persistent hypertension that cannot be controlled; coagulation abnormality on baseline tests; recent major hemorrhage, surgery, or trauma; concomitant severe medical illness; need for contraindicated surgical or medical therapies.
Safety: Symptomatic intracranial hemorrhage (ICH) within 5 days or hospital discharge
Efficacy: Modified Rankin scale score (mRS) score at 3 months
Patients were randomized in a double-blind manner to treatment with abciximab (0.25 mg/kg bolus and 12 hour infusion of 0.125 µg/kg/min; n=200) or placebo (n=200). CT study was repeated at 36-48 hours after study drug infusion. Other antithrombotic agents were not to be used until after study drug discontinuation and after the CT was performed.
The mean time from stroke until treatment with randomized therapy was 5 hours. Mean NIHSS score was 10. Cause of stroke was cardioembolic in 25% of patients, large artery atherosclerosis in 16%, and small vessel occlusion in 12%.
The primary safety endpoint of symptomatic ICH within 5 days or hospital discharge occurred in 3.6% of the abciximab group and 1% of the placebo group (odds ratio [OR] 3.7, p=0.09). TIMI major or minor bleeding occurred in 8 patients in the abciximab group and 3 in the placebo group. Thrombocytopenia during the first 5 days was reported in 3 patients in the abciximab group and 1 in the placebo group. Mortality at 5 days occurred in 8 abciximab patients and 2 placebo patients.
The primary efficacy endpoint of mRS scores at 3 months did not differ between treatment group (OR 1.20, p=0.33). mRS scores of 0 or 1 were present in 48.5% of the abciximab group and 40.0% of the placebo group. NIHSS score of 0 or 1 at 3 months also occurred more frequently in the abciximab group (46% vs 34%, OR 1.65, p=0.01).
Among patients with acute ischemic stroke, treatment with abciximab was not associated with a significant difference in the modified Rankin scale score at 3 months but was associated with a trend toward an increase in ICH within 5 days compared with placebo.
Standard treatment for acute ischemic stroke is use of recombinant tissue plasminogen activator (rtPA). However, rtPA must be administered within 3 hours of the onset of the stroke, which limits its use. Based on the findings of this phase 2 trial, the larger AbESTT II trial was undertaken. The AbESTT II trial was discontinued early due to a high rate of ICH.
Abciximab Emergent Stroke Treatment Trial (AbESTT) Investigators. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of a randomized phase 2 trial. Stroke 2005;36:880-90.
Keywords: Stroke, Atherosclerosis, Platelet Aggregation Inhibitors, Cerebrovascular Disorders, Fibrinolytic Agents, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Thrombocytopenia
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