Low INR to Minimize Bleeding With Mechanical Valves Trial (LIMIT)

Population Health Research Institute (PHRI)

Status and phase: Enrolling; Phase 3

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

Treatments: Drug: Warfarin

Study type: Interventional

Funder types: Other

Identifiers

NCT03636295

5139

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 2,625 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,625 participants in 2 patient groups

Reduced INR Target

Experimental group

Description:

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

Treatment:

Drug: Warfarin

Standard INR Target

Active Comparator group

Description:

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

Treatment:

Drug: Warfarin