A RANDOMIZED, BLINDED STUDY OF 2 DOSES OF NOVASTAN(R) (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(R) AND T-PA (MINT) STUDY

Thrombolytic therapy has become a standard treatment for selected pati ents with acute myocardial infarction (MI). Various thrombolytic agent s have been shown to decrease mortality. However, current thrombolytic agents still suffer significant shortcomings, such as a low optimal r eperfusion 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 imp ortant role. However, it has several features that suggest that it may not be the optimal adjunct to thrombolytics, including weak and indir ect action on thrombin, little access to clot bound thrombin, inhibiti on by acute phase plasma proteins, and its direct stimulation of plate let aggregation. Argatroban (NOVASTAN(R)), a small-molecule, synthetic , direct thrombin inhibitor, has several popotential advantages over h eparin, and prior studies suggest superior thrombin inhibition with fa vorable pharmacokinetic and pharmacodynamic properties warranting furt her investigation. The Myocardial Infarction using NOVASTAN(R) and t-P A (MINT) study is a phase II, single blind, angiographic trial directl y comparing heparin versus two doses of argatroban in 120 patients wit h ST-elevation MI who present within 6 hours of symptom onset. The pri mary objective of the MINT trial is to assess the TIMI grade 3 flow an d TIMI Frame Count at 90 minutes after the initiation of t-PA. This tr ial will also evaluate the safety of the combination of t-PA, argatrob an, and aspirin. The incidence of clinical or silent ischemia will be monitored. All patients will be followed up to 30 days for the composi te endpoint of death, nonfatal recurrent myocardial infarction, corona ry artery bypass surgery, PTCA, recurrent ischemia, and shock/new onse t heart failure.