Clinical trial NCT02565147
Conditions: Acute Myocardial Infarction
Keywords: STEMI, infarct size, CMR, bivalirudin
Sponsor: The Medicines Company
Start date: 2014-12-19; Completion date: 2016-06-14
Enrollment: 78 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate whether the use of bivalirudin will reduce extent of the damage done to the heart muscle in participants who suffered a heart attack, compared to the comparator treatment (heparin).

Detailed description:
The study will assess the effect of bivalirudin administration during primary percutaneous coronary intervention (PPCI) and for 4 hours (h) afterwards, looking at contrast enhanced cardiac magnetic resonance imaging (CMR) assessed infarct size and on circulating markers of thrombosis and cell injury in participants treated with PPCI for a large myocardial infarction (MI).

The objective of this study is to determine whether bivalirudin, compared to heparin \[unfractionated heparin (UFH)\], for PPCI in large ST segment elevation myocardial infarction (STEMI) can:

Primary Objective • Reduce infarct size assessed by CMR 5 days (defined as 5 days ±72 h from randomisation) after PPCI

Secondary Objectives of this study are to determine the effects of bivalirudin compared with UFH treatment for PPCI in STEMI on:

* Other CMR derived parameters of myocardial recovery 5 days after PPCI (that is, left ventricular ejection fraction \[LVEF\], myocardial salvage index \[MSI\], and micro-vascular obstruction \[MVO\])
* LVEF by CMR at 90 days
* Modulate markers of thrombin activity and cell injury after reperfusion
* Coronary flow and micro-circulation at the end of PPCI
* Survival at 90 days

Approximately 200 participants will be randomized. Participants will be stratified prior to randomization: (a) according to total duration of ischemic pain (\<6 h versus ≥6 h); (b) by site.

Diagnosis and Main Criteria for Selection: Adult participants (≥18 years) with an onset of ischemic symptoms of \>20 minutes (min) and \<12 h; a diagnosis of STEMI with ST segment elevation of ≥1 millimeter (mm) in ≥2 contiguous precordial leads, or presumably new left bundle branch block; had thrombolysis in myocardial infarction (TIMI) 0 or 1 flow in the infarct related artery (IRA); fulfilled angiographic criteria/score for a large infarction; and were candidates for PPCI will be enrolled. All participants should receive as soon as logistically feasible: aspirin (150-325 milligrams \[mg\] orally or 250-500 mg intravenously \[IV\]) and a loading dose of any approved P2Y12 inhibitor unless already on maintenance dose.

Bivalirudin will be administered at the time of PPCI at the approved dose of 0.75 mg/kilogram (kg) bolus followed by a 1.75 mg/kg/h infusion that will continue for 4 h after the completion of the index procedure.

Participants randomized to UFH should be treated according to the standard institutional protocol (including the timing and dosing of the UFH bolus). A target activated clotting time (ACT) of ≥250 seconds (s) was recommended.

Criteria for Evaluation:

Primary Endpoint:

• Infarct size assessed by CMR 5 days post-PPCI

Secondary Endpoints:

* CMR MVO assessment at 5 days
* CMR MSI at 5 days
* CMR assessment of LVEF at 5 days
* CMR assessment of LVEF at 90 days
* TIMI flow and Myocardial Blush Grade at end of PPCI
* In-hospital net adverse clinical events up to 5 days or discharge, whichever comes first (death, re-infarction, ischaemia driven revascularization, and Bleeding Academic Research Consortium ≥3 bleeding)
* Death at 90 days

Exploratory assessments:

• Assess patterns between comparator groups at various peri-procedural time points with respect to but not limited to: micro-particle release, thrombin anti thrombin complexes, myeloperoxidase

Sub-study:

• Index microcirculatory resistance

Arms: arm 1: Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure. arm 2: UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
Interventions: intervention 1: PPCI intervention 2: Bivalirudin intervention 3: Heparin
Intervention descriptions: intervention 1: PPCI for treatment of participants presenting with large STEMI. intervention 2: Bivalirudin is an anticoagulant that binds thrombin in a bivalent and reversible fashion and directly inhibits it. intervention 3: Heparin is an anticoagulant.

Protocol documents: