Low INR to Minimize Bleeding With Mechanical Valves Trial

NCT03636295 | Recruiting Phase 3 DMC

• 1 other identifier: 5139
• Study Type: interventional
• Target: 2,625
• Locations: 16 countries
• Sites: 34

Brief Summary

This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical bileaflet heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.

Conditions

Thromboembolism Post-mechanical Valve Replacement; Bleeding Post-mechanical Valve Replacement

Keywords

Mechanical valve replacement; Vitamin K antagonist; INR targets; Bleeding; Thromboembolism

Outcome Measures

Primary Outcomes (2)

• Thrombosis/thromboembolism

  Number of patients who have at least one of the following: ischemic stroke, systemic thromboembolism, and valve thrombosis

  Through study completion, an expected mean of 2-3 years

• Major bleeding

  Number of patients that have bleeding that results in the following: 1. Death and/or, 2. Symptomatic bleeding in critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, in a non-operated joint, or intramuscular with compartment syndrome) and/or, 3. Bleeding that causes drop of hemoglobin level by 20 g/L or more, or that requires the transfusion of 2 or more units of packed red blood cells or whole blood

  Through study completion, an expected mean of 2-3 years

Secondary Outcomes (14)

• All cause mortality

  Through study completion, an expected mean of 2-3 years

• All clinically important bleeding

  Through study completion, an expected mean of 2-3 years

• Minor bleeding

  Through study completion, an expected mean of 2-3 years

• All stroke

  Through study completion, an expected mean of 2-3 years

• Ischemic stroke

  Through study completion, an expected mean of 2-3 years

Study Arms (2)

Reduced INR Target

EXPERIMENTAL

Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5.

Drug: Warfarin

Standard INR Target

ACTIVE COMPARATOR

Warfarin therapy will be titrated to a "standard of care" target INR range.

Drug: Warfarin

Interventions

Warfarin DRUG

Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.

Also known as: Coumadin

Reduced INR Target; Standard INR Target

Eligibility Criteria

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

You may qualify if:

• Age is 18 or older at the time of enrolment
• Have had a bileaflet mechanical heart valve implant in the aortic position 3 or more months ago
• Written informed consent from either the patient or substitute decision maker

You may not qualify if:

• Has a second implanted mechanical valve (any position)
• Lower boundary of planned INR range is less than 2.0
• Pregnant or expecting to become pregnant during the study follow-up

Sponsors & Collaborators

• Population Health Research Institute: lead
• Hamilton Health Sciences Corporation: collaborator

Study Sites (35)

Ziekenhuis Oost-Limburg

Genk, Limburg, 3600, Belgium

RECRUITING

AZ Oostende

Ostend, West-Vlaanderen, 8400, Belgium

RECRUITING

Imelda Hospital

Keerbergen, 2820, Belgium

RECRUITING

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

RECRUITING

University of Botswana, at Princess Marina Hospital

Gaborone, Botswana

RECRUITING

Sociedade Hospitalar Angelina Caron

Campina Grande do Sul, Paraná, 83430-000, Brazil

RECRUITING

HEW Cardiologia LTDA

Joinville, Santa Catarina, 89204-250, Brazil

RECRUITING

InCor-HCFMUSP

Cerqueira César, São Paulo, 05403-000, Brazil

RECRUITING

Fundação Universitária de Cardiologia mantededora do Instituto de Cardiologia e Transplantes do Distrito Federal

Brasília, Brazil

RECRUITING

Dante Pazzanese Institute of Cardiology

São Paulo, Brazil

RECRUITING

St. Elizabeth Catholic General Hospital

Kumbo, Cameroon

RECRUITING

Nova Scotia Health Authority

Halifax, Nova Scotia, B3S 0H6, Canada

NOT YET RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

London Health Sciences Centre Research Inc.

London, Ontario, N6C 2R5, Canada

RECRUITING

The Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Fuwai Hospital, CAMS & PUMC

Beijing, China

RECRUITING

Esbjerg & Grindsted Hospital - University Hospital of Southern Denmark

Esbjerg, Region Syddanmark, 6700, Denmark

RECRUITING

Southern Jutland Hospital

Aabenraa, 6200, Denmark

RECRUITING

Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

Universitätsklinikum Jena

Jena, 07747, Germany

RECRUITING

Città di Lecce Hospital

Lecce, Apulia, 73100, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico Riuniti Foggia

Foggia, 71122, Italy

RECRUITING

Shahid Gangalal National Heart Centre

Kathmandu, Bagmati, 44600, Nepal

RECRUITING

Nobel Medical College and Teaching Hospital

Biratnagar, Koshi, 56613, Nepal

RECRUITING

BP Koirala Institute of Health Sciences

Dharān, Koshi, 56700, Nepal

RECRUITING

Erasmus University Medical Centre

Rotterdam, 3015, Netherlands

RECRUITING

Shifa Clinical Research Center

Islamabad, Capital Territory, 44000, Pakistan

RECRUITING

Meshalkin National Medical Research Center

Novosibirsk, Russia

RECRUITING

King Faisal Specialist Hospital & Research Centre

Riyadh, Saudi Arabia

RECRUITING

Soonchunhyang University Gumi Hospital

Gumi, South Korea

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

RECRUITING

Golden Jubilee National Hospital

Clydebank, Glasgow, G81 4HX, United Kingdom

RECRUITING

Liverpool Heart & Chest Hospital

Liverpool, L143PE, United Kingdom

RECRUITING

South Tees Hospitals NHS Foundation Trust of The James Cook University Hospital

Middlesbrough, United Kingdom

RECRUITING

Related Publications (2)

• Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12.

  PMID: 24512654 BACKGROUND

• Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, De Feo M, Amarelli C, Sasso FC, Salvatore T, Ellison GM, Indolfi C, Cotrufo M, Nappi G. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial. Am Heart J. 2010 Jul;160(1):171-8. doi: 10.1016/j.ahj.2010.05.005.

  PMID: 20598989 BACKGROUND

MeSH Terms

Conditions

Hemorrhage; Thromboembolism

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Emilie Belley-Côté, MD, MSc

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emilie Belley-Côté, MD, MSc

CONTACT

905-527-4322; emilie.belley-cote@phri.ca

Richard Whitlock, MD, PhD

CONTACT

905-527-4322; richard.whitlock@phri.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A prospective, randomized, open-label, blinded end-point (PROBE) clinical trial.

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 17, 2018
• Study Start: September 5, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); NL (1); IT (2); ES (1); RU (1); BR (5); DK (3); CA (5); DE (1); KR (1); BE (4); NE (3); GB (3); PA (1); BO (1); SA (1)