Bivalirudin Infusion for Ventricular Infarction Limitation

NCT02565147 | Terminated Phase 3 Results

• 2 other identifiers: MDCO-BIV-12-022012-002314-39
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 4

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).

Conditions

Acute Myocardial Infarction

Keywords

STEMI, infarct size, CMR, bivalirudin

Outcome Measures

Primary Outcomes (1)

• CMR Assessment Of Infarct Size At Day 5

  Size of cardiac infarct, expressed as grams, as assessed by CMR. The use of CMR has dramatically improved the ability for accurate infarct size estimations and is therefore currently considered the gold standard. The number of participants and their mean reported infarct size, as grams, at Day 5 are presented.

  5 days post PPCI

Secondary Outcomes (7)

• CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5

  5 days post PPCI

• CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5

  5 days post PPCI

• CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5

  5 days post PPCI

• CMR Assessment Of LVEF At Day 90

  90 days post PPCI

• TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI

  1 day (end of PPCI)

Other Outcomes (1)

• Index Of Microcirculatory Resistance (IMR)

  1 day (end of PPCI)

Study Arms (2)

PPCI with Bivalirudin

EXPERIMENTAL

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.

Procedure: PPCI; Drug: Bivalirudin

PPCI with Heparin

ACTIVE COMPARATOR

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.

Procedure: PPCI; Drug: Heparin

Interventions

PPCI PROCEDURE

PPCI for treatment of participants presenting with large STEMI.

PPCI with Bivalirudin; PPCI with Heparin

Bivalirudin DRUG

Bivalirudin is an anticoagulant that binds thrombin in a bivalent and reversible fashion and directly inhibits it.

Also known as: Angiomax, Angiox

PPCI with Bivalirudin

Heparin DRUG

Heparin is an anticoagulant.

Also known as: UFH

PPCI with Heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years
• Experienced ischemic symptoms of \>20 min and \<12 h and had a diagnosis of STEMI with ST segment elevation of ≥1 mm in ≥2 contiguous precordial leads, or presumably new left bundle branch block
• Provided written informed consent or witnessed consent in countries and sites where such participant consenting is applicable, before initiation of any study-related procedures
• Had TIMI 0 or 1 flow in the IRA on initial angiogram
• Fulfilled angiographic criteria/score for a large infarction based on initial angiogram (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease score of ≥21)
• Were candidates for PPCI
• Administration of an initial dose of 150 to 325 mg orally (or 250 to 500 mg IV) and a loading dose of any approved P2Y12 inhibitor

You may not qualify if:

• Contraindication or known hypersensitivity to bivalirudin or UFH
• Refusal to receive blood transfusion/products
• Participants requiring staged coronary artery bypass graft procedure within the first 90 days
• Known international normalized ratio ≥2 or known prothrombin time \>1.5 times upper limit of normal on the day of the index PPCI, or known history of bleeding diathesis
• Therapy with vitamin K antagonists within 72 h of PPCI
• Therapy with dabigatran, rivaroxaban, or other oral anti-Xa or antithrombin agents within 48 h of PPCI
• History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass, aneurysm, arteriovenous malformation, or recent head injury (within the last 5 days)
• Participants with previous history of Q-wave MI
• Known glomerular filtration rate (GFR) \<30 milliliter/min or dialysis dependent
• Major surgery within the previous 30 days
• Upper gastrointestinal or genitourinary bleed 30 days prior to randomization
• Stroke or transient ischemic attack 30 days prior to randomization
• Administration of thrombolytics or glycoprotein IIb/IIIa inhibitor 72 h prior to PPCI
• Administration of enoxaparin 8 h prior to PPCI
• Administration of bivalirudin 12 h prior to PPCI

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (4)

Hopital Ambroise Paré

Boulogne, 92104, France

Location

Hospital Lariboisière

Paris, 75010, France

Location

VUMC Amsterdam

Amsterdam, 1117 HV, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Related Publications (9)

• Alderman EL, Stadius M. The angiographic definitions of the Bypass Angioplasty Revascularization Investigation. Coronary Artery Disease 1992;3: 1189-1207

  BACKGROUND

• Graham MM, Faris PD, Ghali WA, Galbraith PD, Norris CM, Badry JT, Mitchell LB, Curtis MJ, Knudtson ML; APPROACH Investigators (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease. Validation of three myocardial jeopardy scores in a population-based cardiac catheterization cohort. Am Heart J. 2001 Aug;142(2):254-61. doi: 10.1067/mhj.2001.116481.

  PMID: 11479464 BACKGROUND

• Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999 Nov 9;100(19):1992-2002. doi: 10.1161/01.cir.100.19.1992.

  PMID: 10556226 BACKGROUND

• Lowe JE, Reimer KA, Jennings RB. Experimental infarct size as a function of the amount of myocardium at risk. Am J Pathol. 1978 Feb;90(2):363-79.

  PMID: 623206 BACKGROUND

• Ortiz-Perez JT, Meyers SN, Lee DC, Kansal P, Klocke FJ, Holly TA, Davidson CJ, Bonow RO, Wu E. Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging. Eur Heart J. 2007 Jul;28(14):1750-8. doi: 10.1093/eurheartj/ehm212. Epub 2007 Jun 22.

  PMID: 17586811 BACKGROUND

• Reimer KA, Ideker RE, Jennings RB. Effect of coronary occlusion site on ischaemic bed size and collateral blood flow in dogs. Cardiovasc Res. 1981 Nov;15(11):668-74. doi: 10.1093/cvr/15.11.668.

  PMID: 7326685 BACKGROUND

• Seiler C, Kirkeeide RL, Gould KL. Basic structure-function relations of the epicardial coronary vascular tree. Basis of quantitative coronary arteriography for diffuse coronary artery disease. Circulation. 1992 Jun;85(6):1987-2003. doi: 10.1161/01.cir.85.6.1987.

  PMID: 1591819 BACKGROUND

• Seiler C, Kirkeeide RL, Gould KL. Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk. J Am Coll Cardiol. 1993 Mar 1;21(3):783-97. doi: 10.1016/0735-1097(93)90113-f.

  PMID: 8436762 BACKGROUND

• Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet. 2001 Jan 6;357(9249):21-8. doi: 10.1016/S0140-6736(00)03567-4.

  PMID: 11197356 BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

bivalirudin; Heparin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

Since the measured difference in infarct size at Day 5 (by CMR) was \<18%, the study was terminated for futility at the interim analysis as pre-defined in the protocol.

Results Point of Contact

• Title: Global Health Science Center
• Organization: The Medicines Company

medical.information@themedco.com

1.888.977.6326

Study Officials

• Robert J Van Geuns, MD

  Thorax Centrum, Erasmus Medisch Centrum, s-Grave dijkwal 230, 3015 CE Rotterdam, the Netherlands

  PRINCIPAL INVESTIGATOR

• Ludovic Drouet, MD

  Hospital Lariboisiere, Angio-Hematologie, 2 Rue Ambroise Pare, 75475 Paris Cedex 10, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The primary endpoint was evaluated by a core lab totally blinded to clinical information and the treatment groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: October 1, 2015
• Study Start: December 19, 2014
• Primary Completion: June 14, 2016
• Study Completion: June 14, 2016
• Last Updated: October 5, 2018
• Results First Posted: October 5, 2018

Record last verified: 2017-12

Locations

FR (2); NL (2)