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

Joon Bum Kim

Status and phase: Enrolling; Phase 4

Conditions: AORTIC VALVE DISEASES; Thromboembolism

Treatments: Drug: Rivaroxaban Oral Tablet; Drug: Vitamin K antagonist(warfarin)

Study type: Interventional

Funder types: Other

Identifiers

NCT04258488

AMCCV2020-01

Details and patient eligibility

About

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

Enrollment: 1,300 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,300 participants in 2 patient groups

Oral Factor Xa inhibitor

Experimental group

Treatment:

Drug: Rivaroxaban Oral Tablet

Vitamin K antagonist

Active Comparator group

Treatment:

Drug: Vitamin K antagonist(warfarin)