Low INR to Minimize Bleeding With Mechanical Valves Trial

NCT ID: NCT03636295

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2625 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-05

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Warfarin (Coumadin) is a blood thinner used to prevent blood clot formation in patients with mechanical heart valves. Blood clots can block blood flow to the brain, heart, or other parts of the body. Mechanical heart valves increases the risk of clot so patients with a mechanical heart valve must take warfarin to reduce their risk of stroke and other blood clot-related problems.

The degree to which warfarin 'works' varies from person to person, and so dosage is determined by measuring each person's response to the drug as an 'international normalized ratio' or INR. A patient with an INR over 1.0 has blood that takes longer to clot than average, and increasing INR values represent increasing time required for blood to clot. While an INR over 1.0 decreases clotting risk, it also increases bleeding risk. It is important to carefully balance these risks.

Specific INR targets have been recommended for patients with a mechanical heart valve, but these recommendations differ between scientific groups and are based on low quality evidence. Recent studies suggest that a lower INR target range than is currently recommended can be used safely. A laboratory study showed that warfarin effectively prevents blood clot formation on mechanical heart valves as long as the INR is 1.5 or above. Two moderately-sized clinical studies showed that an INR target range of 1.5-2.5 resulted in less bleeding than the usual higher target range without increasing blood clot formation or stroke in patients with a newer valve model. Whether we could use a lower INR target range for patients with a mechanical aortic valve remains controversial.

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

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A prospective, randomized, open-label, blinded end-point (PROBE) clinical trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Reduced INR Target

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

Group Type EXPERIMENTAL

Warfarin

Intervention Type DRUG

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

Standard INR Target

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

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

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

Interventions

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Warfarin

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

Intervention Type DRUG

Other Intervention Names

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Coumadin

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hamilton Health Sciences Corporation

OTHER

Sponsor Role collaborator

Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Emilie Belley-Cote

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Emilie Belley-Côté, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

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Ziekenhuis Oost-Limburg

Genk, Limburg, Belgium

Site Status RECRUITING

AZ Oostende

Ostend, West-Vlaanderen, Belgium

Site Status RECRUITING

Imelda Hospital

Keerbergen, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status RECRUITING

University of Botswana, at Princess Marina Hospital

Gaborone, , Botswana

Site Status RECRUITING

Sociedade Hospitalar Angelina Caron

Campina Grande do Sul, Paraná, Brazil

Site Status RECRUITING

HEW Cardiologia LTDA

Joinville, Santa Catarina, Brazil

Site Status RECRUITING

InCor-HCFMUSP

Cerqueira César, São Paulo, Brazil

Site Status RECRUITING

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

Brasília, , Brazil

Site Status RECRUITING

Dante Pazzanese Institute of Cardiology

São Paulo, , Brazil

Site Status RECRUITING

St. Elizabeth Catholic General Hospital

Kumbo, , Cameroon

Site Status RECRUITING

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Site Status NOT_YET_RECRUITING

Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

London Health Sciences Centre Research Inc.

London, Ontario, Canada

Site Status RECRUITING

The Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Site Status RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

Fuwai Hospital, CAMS & PUMC

Beijing, , China

Site Status RECRUITING

Esbjerg & Grindsted Hospital - University Hospital of Southern Denmark

Esbjerg, Region Syddanmark, Denmark

Site Status RECRUITING

Southern Jutland Hospital

Aabenraa, , Denmark

Site Status RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status RECRUITING

Universitätsklinikum Jena

Jena, , Germany

Site Status RECRUITING

Città di Lecce Hospital

Lecce, Apulia, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Policlinico Riuniti Foggia

Foggia, , Italy

Site Status RECRUITING

Shahid Gangalal National Heart Centre

Kathmandu, Bagmati, Nepal

Site Status RECRUITING

Nobel Medical College and Teaching Hospital

Biratnagar, Koshi, Nepal

Site Status RECRUITING

BP Koirala Institute of Health Sciences

Dharān, Koshi, Nepal

Site Status RECRUITING

Erasmus University Medical Centre

Rotterdam, , Netherlands

Site Status RECRUITING

Shifa Clinical Research Center

Islamabad, Capital Territory, Pakistan

Site Status RECRUITING

Meshalkin National Medical Research Center

Novosibirsk, , Russia

Site Status RECRUITING

King Faisal Specialist Hospital & Research Centre

Riyadh, , Saudi Arabia

Site Status RECRUITING

Soonchunhyang University Gumi Hospital

Gumi, , South Korea

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Golden Jubilee National Hospital

Clydebank, Glasgow, United Kingdom

Site Status RECRUITING

Liverpool Heart & Chest Hospital

Liverpool, , United Kingdom

Site Status RECRUITING

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

Middlesbrough, , United Kingdom

Site Status RECRUITING

Countries

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Belgium Botswana Brazil Cameroon Canada China Denmark Germany Italy Nepal Netherlands Pakistan Russia Saudi Arabia South Korea Spain United Kingdom

Central Contacts

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Emilie Belley-Côté, MD, MSc

Role: CONTACT

905-527-4322 ext. 40306

Richard Whitlock, MD, PhD

Role: CONTACT

905-527-4322 ext. 40306

Facility Contacts

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Philippe Bertrand, MD

Role: primary

Dalton Precoma, MD

Role: primary

Conrado R. Hoffmann Filho, MD

Role: primary

Roney Sampaio, MD

Role: primary

Kaytussia Sena

Role: primary

Mayara Silva

Role: primary

Emilie Belley-Cote, MD

Role: primary

905-527-4322 ext. 40306

Linrui Guo, MD

Role: primary

Joseph Shaw, MD

Role: primary

Mark Blostein, MD

Role: primary

Xiaolu Sun, MD

Role: primary

Alexander Bogachev-Prokophiev, MD

Role: primary

Hun-Gyu Hwang, MD

Role: primary

Ekaterine Popova, MD

Role: primary

Carmen Neave

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 24512654 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20598989 (View on PubMed)

Other Identifiers

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5139

Identifier Type: -

Identifier Source: org_study_id

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