Bleeding Post-mechanical Valve Replacement Clinical Trial
— LIMITOfficial title:
Low INR to Minimize Bleeding With Mechanical Valves Trial
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.
| Status | Recruiting |
| Enrollment | 2625 |
| Est. completion date | December 30, 2026 |
| Est. primary completion date | March 31, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Ziekenhuis Oost-Limburg | Genk | Limburg |
| Belgium | Universitair Ziekenhuis Leuven | Leuven | |
| Brazil | Sociedade Hospitalar Angelina Caron | Campina Grande Do Sul | Parana |
| Brazil | InCor-HCFMUSP | Cerqueira César | São Paulo |
| Brazil | HEW Cardiologia LTDA | Joinville | Santa Catarina |
| Canada | Hamilton General Hospital | Hamilton | Ontario |
| Canada | London Health Sciences Centre Research Inc. | London | Ontario |
| Canada | Jewish General Hospital | Montréal | Quebec |
| Canada | The Ottawa Hospital Research Institute | Ottawa | Ontario |
| Netherlands | Erasmus University Medical Centre | Rotterdam | |
| Russian Federation | Meshalkin National Medical Research Center | Novosibirsk | |
| Spain | Hospital de la Santa Creu i Sant Pau | Barcelona |
| Lead Sponsor | Collaborator |
|---|---|
| Population Health Research Institute | Hamilton Health Sciences Corporation |
Belgium, Brazil, Canada, Netherlands, Russian Federation, Spain,
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | Major bleeding | Number of patients that have bleeding that results in the following:
Death and/or, 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, 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 |
Through study completion, an expected mean of 2-3 years | |
| Secondary | 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 | |
| Secondary | All clinically important bleeding | Number of patients that experience all clinically important bleeding (major and minor) | Through study completion, an expected mean of 2-3 years | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | Systemic thromboembolism | Number of patients who experience a systemic thromboembolism | Through study completion, an expected mean of 2-3 years | |
| Secondary | Valve thrombosis | Number of patients who experience a valve thrombosis | Through study completion, an expected mean of 2-3 years | |
| Secondary | Pulmonary embolism | Number of patients who experience a pulmonary embolism | Through study completion, an expected mean of 2-3 years | |
| Secondary | Deep vein thrombosis | Number of patients who experience a deep vein thrombosis | Through study completion, an expected mean of 2-3 years | |
| Secondary | New renal replacement therapy | Number of patients requiring new renal replacement therapy | Through study completion, an expected mean of 2-3 years | |
| Secondary | 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 | |
| Secondary | 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 |