Comparing blood thinners after mechanical aortic valve replacement

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

This study tests whether a new blood thinner called rivaroxaban works better than the traditional warfarin for people who have had a mechanical aortic valve replacement.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 1300 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Asan Medical Center (other)
• Locations: 15 sites (Bucheon-si and 14 other locations)
• Trial ID: NCT04258488 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of long-term anticoagulation using an oral factor Xa inhibitor, specifically rivaroxaban, compared to the traditional vitamin K antagonist, warfarin, in patients who have undergone mechanical aortic valve replacement. The trial focuses on patients who are at least three months post-surgery and meet specific functional and valve performance criteria. By assessing the outcomes of these two anticoagulation methods, the study aims to determine which is more beneficial for preventing thromboembolism in this patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 19 and older who have undergone mechanical aortic valve replacement at least three months prior and meet specific functional and valve performance criteria.

Not a fit: Patients with old-generation mechanical valves, significant mitral valve issues, or recent history of stroke may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide patients with a more effective and safer anticoagulation option after mechanical aortic valve replacement.

How similar studies have performed: Other studies have shown promising results with factor Xa inhibitors in similar settings, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 19 and more
2. At least 3 months after mechanical aortic valve replacement
3. 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
4. Voluntarily participated in the written agreement

Exclusion Criteria:

1. Old-generation mechanical valve
2. History of mechanical valve implantation in the mitral valve, pulmonary valve, or tricuspid valve
3. Valvular atrial fibrillation(atrial fibrillation with moderate or severe mitral stenosis)
4. Moderate to severe mitral stenosis or regurgitation
5. History of hemorrhagic stroke
6. Clinically overt stroke within the last 3 months
7. Renal failure(creatinine clearance \<15mL/min) or on hemodialysis
8. Left ventricular dysfunction: Left ventricular ejection fraction (LVEF) ≤40%
9. Child-Pugh B and C hepatic impairment or any hepatic disease associated with coagulopathy
10. Clinically significant active bleeding
11. Bleeding or hemorrhagic disorder
12. The increased risk of bleeding due to the following reasons

    1. History of gastrointestinal ulcers or active ulcerations within the last 6 months
    2. History of intracranial or intracerebral hemorrhage within the last 6 months
    3. Spinal cord vascular abnormalities or intracerebral vascular abnormalities
    4. History of the brain, spinal cord, or ophthalmic surgery within the last 6 months
    5. History of the brain or spinal cord injury within the last 6 months
    6. History of the brain or spinal cord injury or spinal tap, major regional anesthesia, or spinal anesthesia within the last 6 months
    7. Esophageal varices
    8. Arteriovenous malformation
    9. Vascular aneurysms
    10. Malignant tumor with a high risk of bleeding
13. Bleeding tendencies associated with overt bleeding of

    1. gastrointestinal, genitourinary, respiratory tract, or colorectal cancer
    2. cerebrovascular hemorrhage
    3. aneurysms- cerebral, dissecting aorta
    4. pericarditis and pericardial effusions
    5. bacterial endocarditis
14. Hemodynamically unstable or pulmonary embolism required thrombolysis or embolectomy
15. 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
16. Uncontrolled moderate or severe hypertension
17. 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
18. Infective endocarditis
19. Hypersensitivity to the main component or constituents of Rivaroxaban or Vitamin K antagonist
20. 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
21. A genetic problem with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
22. The unsuitable condition of the protocol
23. Actively participating in another drug or device investigational study, which has not completed the primary endpoint follow-up period
24. Terminal illness with life expectancy \<12 months
25. Vitamin K deficiency
26. Alcoholic or psychical disorder
27. Threatened abortion, eclampsia, or preeclampsia
28. Concomitant use with antiplatelet in patients with a history of stroke or transient ischemic attack for the treatment of the acute coronary syndrome

Where this trial is running

Bucheon-si and 14 other locations

• Buchen Sejong Hospital — Bucheon-si, South Korea (RECRUITING)
• Seoul National University Bundang Hospital — Bundang, South Korea (NOT_YET_RECRUITING)
• Dong-A University Hospital — Busan, South Korea (RECRUITING)
• Keimyung University Dongsan Hospital — Daegu, South Korea (RECRUITING)
• GangNeung Asan Hospital — Gangneung, South Korea (RECRUITING)
• Chonnam National University Hospital — Gwangju, South Korea (RECRUITING)
• Asan Medical Center — Seoul, South Korea (RECRUITING)
• Korea University Anam Hospital — Seoul, South Korea (RECRUITING)
• Samsung Medical Center — Seoul, South Korea (RECRUITING)
• Seoul National University Hospital — Seoul, South Korea (RECRUITING)
• Ajou University Hospital — Suwon, South Korea (RECRUITING)
• St. Vincent's Hospital, Catholic University of Korea — Suwon, South Korea (NOT_YET_RECRUITING)
• Eulji University Uijeongbu Hospital — Uijeongbu-si, South Korea (NOT_YET_RECRUITING)
• Ulsan University Hospital — Ulsan, South Korea (NOT_YET_RECRUITING)
• Pusan National University Yangsan Hospital — Yangsan, South Korea (RECRUITING)

Study contacts

• Principal investigator: Jung-min Ahn, MD — [e-mail]
• Study coordinator: Jung-hee Ham, RN

Conditions: AORTIC VALVE DISEASES, Thromboembolism, Aortic valve replacement, Mechanical valve