Prospective, Randomized, Double-Blind Multicenter Trial of Single Bolus Injection of the Novel Modified t-P E6010 in the Treatment of Acute Myocardial Infarction: Comparison With Native t-P

Objectives. This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. Background. E6010 is novel modified t-P with prolonged half-life (t1/2 alph ≥23 min) compared with native t-P (t1/2 alph = 4 min). E6010 can be administered in patients as single intravenous bolus injection, and early recanalization can be expected. Methods. The efficacy of E6010 was compared with that of native t-P in 199 patients with acute myocardial infarction who were treated within 6 h of onset in prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-P (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). Results. The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-P group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p = 0.032 at 60 min). Conclusions. The present study indicates that, compared with native t-PA, single bolus injection of E6010 over 2 min produces higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications.