Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement

Study Overview
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Brief Summary
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This study evaluates the long-term anticoagulation with oral factor Xa inhibitor versus vitamin K antagonist in patients receiving a mechanical aortic valve replacement.

Official Title
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Randomized, Evaluation of Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement

Conditions
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AORTIC VALVE DISEASES, Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban Oral Tablet
* Drug: Vitamin K antagonist(warfarin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 and more At least 3 months after mechanical aortic valve replacement At least one of the conditions(as defined below) is met The New York Heart Association (NYHA) Functional Classification I or II; or According to the Valve Academic Research Consortium(VARC)2 criteria, confirmed proper valve function: no prosthesis-patient mismatch and mean aortic valve gradient <20 mm Hg or peak velocity <3 m/s, AND no moderate or severe prosthetic valve regurgitation Voluntarily participated in the written agreement Exclusion Criteria: Old-generation mechanical valve History of mechanical valve implantation in the mitral valve, pulmonary valve, or tricuspid valve Valvular atrial fibrillation(atrial fibrillation with moderate or severe mitral stenosis) Moderate to severe mitral stenosis or regurgitation History of hemorrhagic stroke Clinically overt stroke within the last 3 months Renal failure(creatinine clearance <15mL/min) or on hemodialysis Left ventricular dysfunction: Left ventricular ejection fraction (LVEF) ≤40% Child-Pugh B and C hepatic impairment or any hepatic disease associated with coagulopathy Clinically significant active bleeding Bleeding or hemorrhagic disorder The increased risk of bleeding due to the following reasons History of gastrointestinal ulcers or active ulcerations within the last 6 months History of intracranial or intracerebral hemorrhage within the last 6 months Spinal cord vascular abnormalities or intracerebral vascular abnormalities History of the brain, spinal cord, or ophthalmic surgery within the last 6 months History of the brain or spinal cord injury within the last 6 months History of the brain or spinal cord injury or spinal tap, major regional anesthesia, or spinal anesthesia within the last 6 months Esophageal varices Arteriovenous malformation Vascular aneurysms Malignant tumor with a high risk of bleeding Bleeding tendencies associated with overt bleeding of gastrointestinal, genitourinary, respiratory tract, or colorectal cancer cerebrovascular hemorrhage aneurysms- cerebral, dissecting aorta pericarditis and pericardial effusions bacterial endocarditis Hemodynamically unstable or pulmonary embolism required thrombolysis or embolectomy Combination therapy with other anticoagulants(Unfractionated heparin(UFH), enoxaparin, dalteparin, fondaparinux, etc.) However, the following cases are permitted Switching anticoagulants Intravenous UFH to keep central/arterial lines open Uncontrolled moderate or severe hypertension Anemia at least one among the conditions(as defined below) is met 1) Hemoglobin level <10.0 g/dL or platelet count < 100 x 10x9/L within the last 6 months 2) Diagnosed and documented ongoing anemia Infective endocarditis Hypersensitivity to the main component or constituents of Rivaroxaban or Vitamin K antagonist Positive pregnancy test results (all pregnant women should undergo urinary human chorionic gonadotropin (hCG) testing within 7 days before screening and/or randomization) or during pregnancy or lactation A genetic problem with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption The unsuitable condition of the protocol Actively participating in another drug or device investigational study, which has not completed the primary endpoint follow-up period Terminal illness with life expectancy <12 months Vitamin K deficiency Alcoholic or psychical disorder Threatened abortion, eclampsia, or preeclampsia Concomitant use with antiplatelet in patients with a history of stroke or transient ischemic attack for the treatment of the acute coronary syndrome

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Factor Xa inhibitor<br> | Drug: Rivaroxaban Oral Tablet<br>* For 12months, Rivaroxaban oral tablet 20mg once daily For renal disorder subjects_creatinine clearance 15-49 mL/min, 15mg once daily<br>|
| Active Comparator: Vitamin K antagonist<br> | Drug: Vitamin K antagonist(warfarin)<br>* For 12months, keep the international normalized ratio (INR) 1.7-3.0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with the composite of cardiac death, valve thrombosis, valve-related thromboembolic event, major bleeding, and clinically-relevant non-major bleeding | A composite endpoint is an endpoint that is a combination of multiple clinical endpoints. An event that is considered to have occurred if any one of several different events is observed. Clinically-relevant non-major bleeding is defined as BARC(Bleeding Academic Research Consortium) 2 Bleeding and major Bleeding is defined as BARC(Bleeding Academic Research Consortium) 3 or 5 Bleeding. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With all cause death |  | 1 year | 
| Number of Participants With cardiovascular death |  | 1 year | 
| Number of Participants With valve thrombosis confirmed by transthoracic echocardiography, transesophageal echocardiography, cine fluoroscopy, computed tomography, or autopsy (Valve Academic Research Consortium (VARC ) criteria) |  | 1 year | 
| Number of Participants With valve-related thromboembolic |  | 1 year | 
| Number of Participants With transient ischemic attack |  | 1 year | 
| Number of Participants With stroke |  | 1 year | 
| Number of Participants With systemic embolism |  | 1 year | 
| Number of Participants With myocardial infarction |  | 1 year | 
| Number of Participants With major bleeding | BARC (Bleeding Academic Research Consortium) 3 or 5 | 1 year | 
| Number of Participants With Clinically-relevant non-major bleeding | BARC (Bleeding Academic Research Consortium) 2 | 1 year | 
| Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event |  | 1 year | 
| Number of Participants With the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event |  | 1 year | 
| Number of Participants With the composite event of major bleeding and clinically-relevant non-major bleeding | Clinically-relevant non-major bleeding is defined as BARC (Bleeding Academic Research Consortium) 2 Bleeding and major Bleeding is defined as BARC (Bleeding Academic Research Consortium) 3 or 5 Bleeding. | 1 year | 
| Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event |  | 1 year | 
| Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event |  | 1 year | 
| The change of echocardiographic parameter | Integral ratio at baseline and 1 year follow-up : transaortic valve mean gradient | 1 year | 
| The change of echocardiographic parameter | Integral ratio at baseline and 1 year follow-up : transaortic valve peak gradient | 1 year | 
| The change of echocardiographic parameter | Integral ratio at baseline and 1 year follow-up : transaortic valve peak velocity | 1 year | 
| The change of echocardiographic parameter | Integral ratio at baseline and 1 year follow-up : effective orifice area(EOA) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve replacement, Mechanical valve