OPEN, NONCONTROLLED DOSE-FINDING STUDY WITH A NOVEL RECOMBINANT PLASMINOGEN-ACTIVATOR (BM 06.022) GIVEN AS A DOUBLE BOLUS IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mu tant of tissue-type plasminogen activator expressed in escherichia cel l which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an in travenous r-PA double bolus (first bolus of 10 MU followed by 5 MU aft er 30 minutes) in patients with acute myocardial infarction. All patie nts received heparin intravenously and acetylsalicylic acid orally. Ef ficacy was assessed from infarct artery patency by coronary angiograph y (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3 ) in SO patients. Ninety minutes after administration of the first r-P A bolus, the infarct-related coronary artery was patent in 39 of 50 pa tients (78%; 95% confidence interval 64 to 88%). An angiographically c onfirmed reocclusion occurred in 1 patient between 90 minutes and 24 t o 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic par ameters showed a decrease in fibrinogen to 37% of baseline value. Ther e were 3 dinical reinfarctions before discharge and 2 major puncture s ite hemorrhages. No further serious bleeding and no serious adverse ev ent with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regi men appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limit ed number of patients treated in this study, one need not be concerned about the safety profile of r-PA.