Bleeding Post-mechanical Valve Replacement, Thromboembolism Post-mechanical Valve Replacement
Conditions
Keywords
Mechanical valve replacement, Vitamin K antagonist, INR targets, Bleeding, Thromboembolism
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.
Interventions
DRUGWarfarin
Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.
Sponsors
Population Health Research Institute
Hamilton Health Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A prospective, randomized, open-label, blinded end-point (PROBE) clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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 |
Countries
Belgium, Botswana, Brazil, Cameroon, Canada, China, Denmark, Germany, Italy, Kenya, Nepal, Netherlands, Pakistan, Russia, Saudi Arabia, South Korea, Spain, United Kingdom
Contacts
CONTACTEmilie Belley-Côté, MD, MSc
CONTACTRichard Whitlock, MD, PhD
PRINCIPAL_INVESTIGATOREmilie Belley-Côté, MD, MSc
McMaster University
Outcome results
None listed