Skip to main content
OpenTrials
Recruiting

NCT Number: NCT03636295

Low INR to Minimize Bleeding With Mechanical Valves Trial

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Bleeding Post-mechanical Valve Replacement Cardiovascular Diseases Embolism and Thrombosis Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms Thromboembolism Thromboembolism Post-mechanical Valve Replacement Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Ziekenhuis Oost-Limburg, Genk, Limburg, Belgium

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: Coumadin

Primary outcomes

  1. Thrombosis/thromboembolism

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

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

  2. Major bleeding

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

    Number of patients that have bleeding that results in the following:

    • Death and/or,
    • 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,
    • 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

Secondary outcomes

  1. All cause mortality

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

    Selected rather than cardiovascular mortality, as cause-specific mortality is often difficult to ascertain or define in complex cardiovascular patients in whom multi-end-organ dysfunction may accompany cardiovascular decline.

  2. All clinically important bleeding

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

    Number of patients that experience all clinically important bleeding (major and minor)

  3. Minor bleeding

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

    Number of patients that experience a bleed that does not meet major bleeding criteria

  4. All stroke

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

    Number of patients that experience a strokes, including ischemic stroke, ischemic with secondary transformation, stroke of uncertain classification and hemorrhagic stroke

  5. Ischemic stroke

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

    Number of patients that experience an ischemic stroke, defined as focal brain infarction caused by an arterial (or rarely venous) obstruction and as documented by CT/MRI that is normal or shows an infarct in the clinicall expected area

  6. Hemorrhagic stroke

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

    Number of patients that experience a hemorrhagic stroke, defined as requiring neuroimaging or autopsy confirmation, and includes two subcategories: primary intracerebral hemorrhage and primary subarachnoid hemorrhage

  7. Type 1, 2 or 3 myocardial infarction

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

    Number of patients who experience a type 1, 2 or 3 myocardial infarction

  8. Systemic thromboembolism

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

    Number of patients who experience a systemic thromboembolism

  9. Valve thrombosis

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

    Number of patients who experience a valve thrombosis

  10. Pulmonary embolism

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

    Number of patients who experience a pulmonary embolism

  11. Deep vein thrombosis

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

    Number of patients who experience a deep vein thrombosis

  12. New renal replacement therapy

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

    Number of patients requiring new renal replacement therapy

  13. Time in therapeutic range

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

    The percentage of time the patient's INR was within the target range

  14. Proportion of patients with extreme INR values (>4)

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

    The proportion of patients with at least one reported INR value above 4

Study contacts

Contact information is provided by the study sponsor or research team.

Emilie Belley-Côté, MD, MSc

CONTACT

[email protected]

905-527-4322 ext. 40306

Richard Whitlock, MD, PhD

CONTACT

[email protected]

905-527-4322 ext. 40306

Sponsors and collaborators

Lead sponsor

Population Health Research Institute

Other

Collaborators

  • Hamilton Health Sciences Corporation

Registry information

Acronym: LIMIT

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Aug 17, 2018
Registry last updated
Jan 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.