Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke–Enhanced Regimen Stroke Trial (CLEAR-ER) trial

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Pancioli and colleague’s present data from the Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke–Enhanced Regimen (CLEAR-ER) trial,which was a multicenter, double-blind, randomized safety study designed to provide data concerning the risks and benefits of combining eptifibatide, a glycoprotein IIb/IIIa antagonist, with intravenous recombinant tissue-type plasminogen activator (rt-PA) to treat acute ischemic stroke patients within 3 hours of symptom onset.Patients were randomized 5:1 to the combination of medium dose rt-PA (0.6 mg/kg) plus eptifibatide (135 μg/kg bolus followed by a 2-hour infusion at 0.75μg/kg per minute) versus standard dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial haemorrhage (sICH [defined as any intracranial haemorrhage related to a decline in neurological status]) within 36 hours of treatment. The primary efficacy outcome measure was a modified Rankin Scale (mRS) score 1 or return to baseline mRS at 90 days. The study enrolled 126 subjects from July 2009 to October 2012; 101 received the combination therapy, and 25 received standard dose rt-PA. Although not significantly different, patients randomized to the combination group had a lower median National Institutes of Health Stroke Scale score, presented earlier, and were treated a little earlier than those randomized to standard therapy. The sICH rates were 2% in the combination group and 12% in the standard treatment arm (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.01–1.40;P=0.053). Mild and moderate systemic bleeding was more common in the combination therapy group, but there was no difference in life-threatening systemic bleeding. At 90 days after treatment, 49.5% of the combination treatment group patients had a mRS≤1 or return to baseline mRS compared with 36.0% in the standard treatment group (adjusted OR, 1.38; 95% CI, 0.51–3.76;P=0.52).

the presented data highlight feasibility and reasonable safety of combination therapy, which may pave the way for a larger phase III trial.