901-2 Randomized, Double-Blind Multicenter Trial of a Novel Modified t-PA, E6010 by i.v. Bolus Injection in Treatment of Acute Myocardial Infarction (AMI) – Comparison with Native t-PA

Abstract

E6010 is a novel modified t-PA, in which cysteine 84 in the epidermal growth factor domain has been replaced by serine.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-PA to be effective by i.v. bolus injection, and it has a prolonged half-life (Tα1/2 > 20 min) compared to native t-PA. A randomized, double-blind multicenter trial of i.v. bolus injection of E601 0, 27,500 EU/kg, compared with native t-PA (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. % Recanalization Rate (TIMI grade 2 or 3) 15 min. 30 min. 45 min 60 min. E6010 n = 97 36.5 61.9 73.7 79.4 native t-PA n = 102 13.7 32.4 49.5 64.7 The time to reperfusion with E601 0 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 E601 0.4 patients (3.8%) in E6010 and 3 patients (2.8%) in native t-PA died during 48 days post treatment hospitalization. Native t-PA 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 E601 0 can be easily administered by i.v. bolus injection taking 2–3 minutes and it exerts a valuable thrombolytic effects, namely a high rate and early recanalization of infarct-related arteries