Overview

This trial is active, not recruiting.

Condition acute myocardial infarction
Treatments primary pci, bivalirudin
Phase phase 3
Sponsor The Medicines Company
Start date November 2014
End date June 2016
Trial size 78 participants
Trial identifier NCT02565147, MDCO-BIV-12-02

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 patients who suffered a heart attack, compared to the comparator treatment (heparin).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Heparin to be dosed according to standard of care for completion of PCI per site. An ACT>250 at the end of the procedure is recommended.
primary pci
Primary PCI for treatment of patients presenting with STEMI
(Experimental)
Bivalirudin given as a bolus (0.75mg/kg) followed by 4 hr infusion after the completion of primary PCI using the PCI dose (1.75mg/kg/h)
primary pci
Primary PCI for treatment of patients presenting with STEMI
bivalirudin Angiomax, Angiox
prolonged infusion of bivalirudin with a dose already included in the SmPC to assess it's impact on infarct size compared to standard dose of heparin

Primary Outcomes

Measure
Infarct size assessed by CMR expressed in grams
time frame: at day 5 post primary PCI

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. ≥ 18 years 2. Experience ischemic symptoms of >20 min and <12 h and have a diagnosis of STEMI with ST segment elevation of ≥1 mm in ≥2 contiguous precordial leads, or presumably new left bundle branch block 3. 3. Provide written informed consent or witnessed consent in countries and sites where such patient consenting is applicable, before initiation of any study -related procedures 4. Have TIMI 0 or 1 flow in the IRA on initial angiogram 5. Fulfill angiographic criteria/score for a large infarction based on initial angiogram (APPROACH score of ≥21; see Appendix 1) 6. Are candidates for PPCI 7. Administration of an initial dose of 150-325 mg orally (or 250-500 mg IV) and a loading dose of any approved P2Y12 inhibitor Exclusion Criteria: 1. Contraindication or known hypersensitivity to bivalirudin or UFH 2. Refusal to receive blood transfusion/products 3. Subjects requiring staged coronary artery bypass graft (CABG) procedure within the first 90 days 4. Known international normalized ratio (INR) ≥ 2 or known prothrombin time (PT) >1.5 times upper limit of normal on the day of the index PPCI, or known history of bleeding diathesis 5. Therapy with vitamin K antagonists (VKA), within 72 h of PPCI 6. Therapy with dabigatran, rivaroxaban or other oral anti-Xa or antithrombin agents within 48 h of PPCI 7. History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass, aneurysm, arteriovenous malformation, or recent head injury (within the last 5 days) 8. Subjects with previous history of Q-wave MI 9. Known glomerular filtration rate (GFR) <30 milliliter (mL)/minute (min) or dialysis dependent 10. Major surgery within the previous 30 days 11. Minor surgery/biopsy exclusions in the past 3 days 12. Upper gastrointestinal or genitourinary bleed 30 days prior to randomization 13. Stroke or transient ischemic attack 30 days prior to randomization 14. Administration of thrombolytics or GPI 72 h prior to PPCI 15. Administration of enoxaparin 8 h prior to PPCI 16. Administration of bivalirudin 12 h prior to PPCI 17. Administration of fondaparinux or other LMWH 24 h prior to PPCI 18. Known contraindications to aspirin or P2Y12 inhibitors 19. Known allergy that cannot be pre-medicated to iodinated contrast 20. Known contraindication to CMR 21. Women of child bearing potential1 22. Previous enrolment in this study 23. Treatment with other investigational drugs or devices within the 30 days preceding enrolment or planned use of other investigational drugs or devices before the primary endpoint of this study has been reached 24. Patients with a body weight > 150 kg Child bearing potential is defined as: A female patient is considered to have childbearing potential unless she meets at least one of the following criteria: - Age ≥50 years and naturally amenorrhoeic for ≥ 1 year*. - Premature ovarian failure confirmed by a specialist gynaecologist. - Previous bilateral salpingo‐oophorectomy, or hysterectomy. - XY genotype, Turner's syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential.

Additional Information

Official title Bivalirudin Infusion for Ventricular Infarction Limitation
Principal investigator Robert J Van Geuns, MD
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 subjects treated with PPCI for a large myocardial infarction (MI). The objective of this study is to determine whether bivalirudin, compared to unfractionated heparin (UFH), for primary percutaneous coronary intervention (PPCI) in large ST segment elevation myocardial infarction (STEMI) can: Primary Objective - Reduce infarct size assessed by cardiac magnetic resonance imaging (CMR) at 5 (defined as 5 days ± 36 h from randomisation) days after PPCI Secondary Objectives - Improve other CMR derived parameters of myocardial recovery 5 days after PPCI (i.e. left ventricular ejection fraction [LVEF], myocardial salvage index [MSI] and micro-vascular obstruction [MVO]). - Improve LVEF by CMR at 90 days - Modulate markers of thrombin activity and cell injury after reperfusion Approximately 200 subjects will be randomized. Subjects will be stratified prior to randomization according to: a) total duration of ischemic pain (< 6 h vs. ≥6 h), and b) by site. Diagnosis and Main Criteria for Selection: Adult subjects (≥18 years) with an onset of symptoms of >20 minutes (min) and <12 h will be enrolled based on a diagnosis of STEMI with ST segment elevation of ≥1 mm in ≥2 contiguous precordial leads, or presumably new left bundle branch block and who have Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow in the infarct related artery (IRA) and fulfill angiographic criteria/score for a large infarction and are candidates for PPCI. All subjects 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/kg bolus followed by a 1.75 mg/kg/h infusion that will continue for 4 h after the completion of the index procedure. Subjects randomized to UFH should be treated according to the institutional protocol (including the timing and dosing of the UFH bolus). A target activated clotting time (ACT) of ≥250 seconds (s) is 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 (MBG) at end of PPCI - In-hospital net adverse clinical events (NACE) up to 5 days or discharge, whichever comes first (death, re-infarction, ischaemia driven revascularisation [IDR], and Bleeding Academic Research Consortium [BARC] ≥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 (TAT), myeloperoxidase (MPO) Sub-study: • Index microcirculatory resistance (IMR) and collateral flow index (CFI) sub-study
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by The Medicines Company.