A randomized, blinded study of two doses of Novastan® (brand of argatroban) versus heparin as adjunctive therapy to recombinant tissue plasminogen activator (accelerated administration) in acute myocardial infarction:: Rationale and design of the myocardial infarction using Novastan® and t-PA (MINT) study

Thrombolytic therapy has become a standard treatment for selected patients with acute myocardial infarction (MI). Various thrombolytic agents have been shown to decrease mortality. However, current thrombolytic agents still suffer significant shortcomings, such as a low optimal reperfusion fusion rate, delayed reperfusion, and incomplete myocardial perfusion. Furthermore, cyclic flow variations and reocclusion remain a significant cause of late morbidity and mortality. In thrombolysis with tissue plasminogen activator (t-PA), heparin seems to play an important role. However, it has several features that suggest that it may not be the optimal adjunct to thrombolytics, including weak and indirect action on thrombin, little access to clot bound thrombin, inhibition by acute phase plasma proteins, and its direct stimulation of platelet aggregation. Argatroban (NOVASTAN(R)), a small-molecule, synthetic, direct thrombin inhibitor, has several popotential advantages over heparin, and prior studies suggest superior thrombin inhibition with favorable pharmacokinetic and pharmacodynamic properties warranting further investigation. The Myocardial Infarction using NOVASTAN(R) and t-PA (MINT) study is a phase II, single blind, angiographic trial directly comparing heparin versus two doses of argatroban in 120 patients with ST-elevation MI who present within 6 hours of symptom onset. The primary objective of the MINT trial is to assess the TIMI grade 3 flow and TIMI Frame Count at 90 minutes after the initiation of t-PA. This trial will also evaluate the safety of the combination of t-PA, argatroban, and aspirin. The incidence of clinical or silent ischemia will be monitored. All patients will be followed up to 30 days for the composite endpoint of death, nonfatal recurrent myocardial infarction, coronary artery bypass surgery, PTCA, recurrent ischemia, and shock/new onset heart failure.