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| Name | Class |
|---|---|
| Hamilton Health Sciences Corporation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced INR Target | Experimental | Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5. |
|
| Standard INR Target | Active Comparator | Warfarin therapy will be titrated to a "standard of care" target INR range. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Thrombosis/thromboembolism | Number of patients who have at least one of the following: ischemic stroke, systemic thromboembolism, and valve thrombosis | Through study completion, an expected mean of 2-3 years |
| Major bleeding | Number of patients that have bleeding that results in the following:
| Through study completion, an expected mean of 2-3 years |
| Measure | Description | Time Frame |
|---|---|---|
| All cause mortality | 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. | Through study completion, an expected mean of 2-3 years |
| All clinically important bleeding |
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Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Emilie Belley-Côté, MD, MSc | Contact | 905-527-4322 | 40306 | emilie.belley-cote@phri.ca |
| Richard Whitlock, MD, PhD | Contact | 905-527-4322 | 40306 | richard.whitlock@phri.ca |
| Name | Affiliation | Role |
|---|---|---|
| Emilie Belley-Côté, MD, MSc | McMaster University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ziekenhuis Oost-Limburg | Recruiting | Genk | Limburg | 3600 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24512654 | Background | Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12. | |
| 20598989 |
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We will establish a plan for the full-scale study but there is no plan to make IPD available to other researchers.
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A prospective, randomized, open-label, blinded end-point (PROBE) clinical trial.
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|
Number of patients that experience all clinically important bleeding (major and minor) |
| Through study completion, an expected mean of 2-3 years |
| Minor bleeding | Number of patients that experience a bleed that does not meet major bleeding criteria | Through study completion, an expected mean of 2-3 years |
| All stroke | Number of patients that experience a strokes, including ischemic stroke, ischemic with secondary transformation, stroke of uncertain classification and hemorrhagic stroke | Through study completion, an expected mean of 2-3 years |
| Ischemic stroke | 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 | Through study completion, an expected mean of 2-3 years |
| Hemorrhagic stroke | 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 | Through study completion, an expected mean of 2-3 years |
| Type 1, 2 or 3 myocardial infarction | Number of patients who experience a type 1, 2 or 3 myocardial infarction | Through study completion, an expected mean of 2-3 years |
| Systemic thromboembolism | Number of patients who experience a systemic thromboembolism | Through study completion, an expected mean of 2-3 years |
| Valve thrombosis | Number of patients who experience a valve thrombosis | Through study completion, an expected mean of 2-3 years |
| Pulmonary embolism | Number of patients who experience a pulmonary embolism | Through study completion, an expected mean of 2-3 years |
| Deep vein thrombosis | Number of patients who experience a deep vein thrombosis | Through study completion, an expected mean of 2-3 years |
| New renal replacement therapy | Number of patients requiring new renal replacement therapy | Through study completion, an expected mean of 2-3 years |
| Time in therapeutic range | The percentage of time the patient's INR was within the target range | Through study completion, an expected mean of 2-3 years |
| Proportion of patients with extreme INR values (>4) | The proportion of patients with at least one reported INR value above 4 | Through study completion, an expected mean of 2-3 years |
| AZ Oostende | Recruiting | Ostend | West-Vlaanderen | 8400 | Belgium |
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| Imelda Hospital | Recruiting | Keerbergen | 2820 | Belgium |
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| Universitair Ziekenhuis Leuven | Recruiting | Leuven | 3000 | Belgium |
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| University of Botswana, at Princess Marina Hospital | Recruiting | Gaborone | Botswana |
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| Sociedade Hospitalar Angelina Caron | Recruiting | Campina Grande do Sul | Paraná | 83430-000 | Brazil |
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| HEW Cardiologia LTDA | Recruiting | Joinville | Santa Catarina | 89204-250 | Brazil |
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| InCor-HCFMUSP | Recruiting | Cerqueira César | São Paulo | 05403-000 | Brazil |
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| Fundação Universitária de Cardiologia mantededora do Instituto de Cardiologia e Transplantes do Distrito Federal | Recruiting | Brasília | Brazil |
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| Dante Pazzanese Institute of Cardiology | Recruiting | São Paulo | Brazil |
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| St. Elizabeth Catholic General Hospital | Recruiting | Kumbo | Cameroon |
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| Nova Scotia Health Authority | Not yet recruiting | Halifax | Nova Scotia | B3S 0H6 | Canada |
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| Hamilton General Hospital | Recruiting | Hamilton | Ontario | L8L 2X2 | Canada |
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| London Health Sciences Centre Research Inc. | Recruiting | London | Ontario | N6C 2R5 | Canada |
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| The Ottawa Hospital Research Institute | Recruiting | Ottawa | Ontario | K1H 8L6 | Canada |
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| Jewish General Hospital | Recruiting | Montreal | Quebec | H3T 1E2 | Canada |
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| Fuwai Hospital, CAMS & PUMC | Recruiting | Beijing | China |
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| Esbjerg & Grindsted Hospital - University Hospital of Southern Denmark | Recruiting | Esbjerg | Region Syddanmark | 6700 | Denmark |
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| Southern Jutland Hospital | Recruiting | Aabenraa | 6200 | Denmark |
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| Aarhus University Hospital | Recruiting | Aarhus | 8200 | Denmark |
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| Universitätsklinikum Jena | Recruiting | Jena | 07747 | Germany |
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| Città di Lecce Hospital | Recruiting | Lecce | Apulia | 73100 | Italy |
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| Azienda Ospedaliero Universitaria Policlinico Riuniti Foggia | Recruiting | Foggia | 71122 | Italy |
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| Shahid Gangalal National Heart Centre | Recruiting | Kathmandu | Bagmati | 44600 | Nepal |
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| Nobel Medical College and Teaching Hospital | Recruiting | Biratnagar | Koshi | 56613 | Nepal |
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| BP Koirala Institute of Health Sciences | Recruiting | Dharān | Koshi | 56700 | Nepal |
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| Erasmus University Medical Centre | Recruiting | Rotterdam | 3015 | Netherlands |
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| Shifa Clinical Research Center | Recruiting | Islamabad | Capital Territory | 44000 | Pakistan |
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| Meshalkin National Medical Research Center | Recruiting | Novosibirsk | Russia |
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| King Faisal Specialist Hospital & Research Centre | Recruiting | Riyadh | Saudi Arabia |
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| Soonchunhyang University Gumi Hospital | Recruiting | Gumi | South Korea |
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| Hospital de la Santa Creu i Sant Pau | Recruiting | Barcelona | 08025 | Spain |
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| Golden Jubilee National Hospital | Recruiting | Clydebank | Glasgow | G81 4HX | United Kingdom |
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| Liverpool Heart & Chest Hospital | Recruiting | Liverpool | L143PE | United Kingdom |
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| South Tees Hospitals NHS Foundation Trust of The James Cook University Hospital | Recruiting | Middlesbrough | United Kingdom |
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| Background |
| Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, De Feo M, Amarelli C, Sasso FC, Salvatore T, Ellison GM, Indolfi C, Cotrufo M, Nappi G. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial. Am Heart J. 2010 Jul;160(1):171-8. doi: 10.1016/j.ahj.2010.05.005. |
| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D013923 | Thromboembolism |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D014859 | Warfarin |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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