Randomized, Double-Blind Multicenter Trial of Novel Modified t-PA, E6010 by i.v. Bolus Injection in Treatment of Acute Myocardial Infarction (AMI) -- Comparison with Native t-PA

E6010 is novel modified t-PA, in which cysteine 84 in the epidermal growth factor domain has been replaced by serine. This is the first modified t-P to be effective by i.v. bolus injection, and it has prolonged half-life (Tα > 20 min) compared to native t-PA. randomized, double-blind multicenter trial of i.v. bolus injection of E6010, 27,500 EU/kg, compared with native t-P (cell culture), 14,400,000 IU has been performed in the treatment of AMI of ≤6 hr duration and total occlusion of the infarct-related arteries. Angiograms were used to evaluate the patency of infarct-related arteries at 15, 30, 45, and 60 minutes after the administration. Result: The time to reperfusion with E6010 was shorter than that with native t-PA. Coronary recanalization at 30 and 60 minutes after administration was obtained in 61.9% and 79.4% of the case with E6010 and in 32.4% and 64.7% of the case with native t-PA, and the difference between both were statistically significant. No fatal bleeding complications were observed in E6010. 4 patients (3.8%) in E6010 and 3 patients (2.8%) in native t-P died during 48 days post treatment hospitalization. Discussion and Conclusion: Native t-P is required to be administered over period of 1 hr with 10% of the total dose administered as an i.v. bolus and the remainder infused i.v. over 1 hr. Our present results indicate that E6010 can be easily administered by i.v. bolus injection taking 2-3 minutes and it exerts valuable thrombolytic effects, namely high rate and early recanalization of infarct-related arteries.