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

Am J Cardiol. 1993 Sep 1;72(7):518-24. doi: 10.1016/0002-9149(93)90345-d.

Abstract

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli 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 intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Enzyme Tests
  • Coronary Angiography
  • Electrocardiography / drug effects
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Germany
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recurrence
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects

Substances

  • Fibrinolytic Agents
  • Recombinant Proteins
  • reteplase
  • Tissue Plasminogen Activator