Low INR to Minimize Bleeding With Mechanical Valves Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 2,625
- Locations
- 67
- Primary Endpoint
- Thrombosis/thromboembolism
Study Overview
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Reduced INR Target
Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5.
Intervention: Warfarin (Drug)
Standard INR Target
Warfarin therapy will be titrated to a "standard of care" target INR range.
Intervention: Warfarin (Drug)
Outcomes
Primary Outcomes
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
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: 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
Secondary Outcomes
- All cause mortality(Through study completion, an expected mean of 2-3 years)
- Ischemic stroke(Through study completion, an expected mean of 2-3 years)
- Hemorrhagic stroke(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)
- Type 1, 2 or 3 myocardial infarction(Through study completion, an expected mean of 2-3 years)
- Systemic thromboembolism(Through study completion, an expected mean of 2-3 years)
- Valve thrombosis(Through study completion, an expected mean of 2-3 years)
- Pulmonary embolism(Through study completion, an expected mean of 2-3 years)
- Deep vein thrombosis(Through study completion, an expected mean of 2-3 years)
- New renal replacement therapy(Through study completion, an expected mean of 2-3 years)
- Time in therapeutic range(Through study completion, an expected mean of 2-3 years)
- Proportion of patients with extreme INR values (>4)(Through study completion, an expected mean of 2-3 years)
Investigators
Emilie Belley-Cote
Principal Investigator
Population Health Research Institute