NCT02565147

Bivalirudin Infusion for Ventricular Infarction Limitation

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: The Medicines Company · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Conditions

• Acute Myocardial Infarction

Interventions

Type	Name	Description
PROCEDURE	PPCI	PPCI for treatment of participants presenting with large STEMI.
DRUG	Bivalirudin	Bivalirudin is an anticoagulant that binds thrombin in a bivalent and reversible fashion and directly inhibits it.
DRUG	Heparin	Heparin is an anticoagulant.

Timeline

• Start date: 2014-12-19
• Primary completion: 2016-06-14
• Completion: 2016-06-14
• First posted: 2015-10-01
• Last updated: 2018-10-05
• Results posted: 2018-10-05

Locations

4 sites across 2 countries: France, Netherlands