Abciximab in acute ischemic stroke. A randomized, double-blind, placebo-controlled, dose-escalation study. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of a randomized phase 2 trial.
Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data.
                We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months.
                There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post-study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index > or =95 or modified Rankin scale < or =1) among abciximab patients compared with those who received placebo.
                Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome. Because of its success in treatment of acute cardiac ischemia, there is interest in the use of abciximab for treating patients with acute ischemic stroke. A previous dose-escalation study determined that abciximab could be given safely in a regimen of 0.25 mg/kg intravenous bolus followed by a 12-hour infusion at 0.125 microg/kg per minute (maximum 10 microg/min). This study was performed to obtain more information about the safety and potential efficacy of abciximab in patients with stroke.
                An international randomized, double-blind, placebo-controlled phase 2 trial enrolled 400 patients within 6 hours of onset of ischemic stroke. The primary safety outcome was the rate of symptomatic hemorrhage that occurred during the first 5 days after stroke. The primary efficacy measure was the distribution of outcomes at 3 months after stroke using the modified Rankin Scale (mRS) based on an ordinal regression model of outcomes, adjusting for baseline severity of stroke, age, and interval from stroke.
                Symptomatic intracranial hemorrhage within 5 days was diagnosed in 7 of 195 (3.6%) patients treated with abciximab and 2 of 199 (1%) patients given placebo (odds ratio [OR], 3.7; P=0.09; 95% confidence interval [CI], 0.7 to 25.9). Asymptomatic hemorrhagic transformation was detected by brain imaging in 24 patients administered abciximab and 33 patients receiving placebo (OR, 0.74; P=0.25; 95% CI, 0.4 to 1.3). Treatment with abciximab showed a nonsignificant shift in favorable outcomes as measured by mRS scores at 3 months (OR, 1.20; P=0.33; 95% CI, 0.84 to 1.70).
                Intravenously administered abciximab can be given to patients with a reasonable degree of safety. The trial also suggests that abciximab could improve outcomes at 3 months after stroke. A larger randomized, double-blind, placebo-controlled trial is necessary to test the efficacy of abciximab.