Low INR to Minimize Bleeding With Mechanical Valves Trial
- Conditions
- Thromboembolism Post-mechanical Valve ReplacementBleeding Post-mechanical Valve Replacement
- Interventions
- Registration Number
- NCT03636295
- Lead Sponsor
- Population Health Research Institute
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2625
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reduced INR Target Warfarin Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5. Standard INR Target Warfarin Warfarin therapy will be titrated to a "standard of care" target INR range.
- Primary Outcome Measures
Name Time Method Thrombosis/thromboembolism 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 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 Outcome Measures
Name Time Method All cause mortality 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.
Ischemic stroke 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
Hemorrhagic stroke 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
All clinically important bleeding Through study completion, an expected mean of 2-3 years Number of patients that experience all clinically important bleeding (major and minor)
Minor bleeding Through study completion, an expected mean of 2-3 years Number of patients that experience a bleed that does not meet major bleeding criteria
All stroke 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
Type 1, 2 or 3 myocardial infarction Through study completion, an expected mean of 2-3 years Number of patients who experience a type 1, 2 or 3 myocardial infarction
Systemic thromboembolism Through study completion, an expected mean of 2-3 years Number of patients who experience a systemic thromboembolism
Valve thrombosis Through study completion, an expected mean of 2-3 years Number of patients who experience a valve thrombosis
Pulmonary embolism Through study completion, an expected mean of 2-3 years Number of patients who experience a pulmonary embolism
Deep vein thrombosis Through study completion, an expected mean of 2-3 years Number of patients who experience a deep vein thrombosis
New renal replacement therapy Through study completion, an expected mean of 2-3 years Number of patients requiring new renal replacement therapy
Time in therapeutic range Through study completion, an expected mean of 2-3 years The percentage of time the patient's INR was within the target range
Proportion of patients with extreme INR values (>4) Through study completion, an expected mean of 2-3 years The proportion of patients with at least one reported INR value above 4
Trial Locations
- Locations (12)
Erasmus University Medical Centre
🇳🇱Rotterdam, Netherlands
InCor-HCFMUSP
🇧🇷Cerqueira César, São Paulo, Brazil
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
Ziekenhuis Oost-Limburg
🇧🇪Genk, Limburg, Belgium
HEW Cardiologia LTDA
🇧🇷Joinville, Santa Catarina, Brazil
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Sociedade Hospitalar Angelina Caron
🇧🇷Campina Grande Do Sul, Parana, Brazil
Meshalkin National Medical Research Center
🇷🇺Novosibirsk, Russian Federation
London Health Sciences Centre Research Inc.
🇨🇦London, Ontario, Canada
The Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada