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

Phase 4

Recruiting

• Conditions: AORTIC VALVE DISEASES; Thromboembolism
• Interventions: Drug: Rivaroxaban Oral Tablet; Drug: Vitamin K antagonist(warfarin)

• Registration Number: NCT04258488
• Lead Sponsor: Joon Bum Kim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-03
• Study First Submitted QC: 2020-02-04
• Study First Posted: 2020-02-06
• Study Start: 2022-02-21
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-04
• Last Update Posted: 2024-07-08
• Primary Completion: 2024-12-31
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Factor Xa inhibitor	Rivaroxaban Oral Tablet	-
Vitamin K antagonist	Vitamin K antagonist(warfarin)	-

Primary Outcome Measures

Name	Time	Method
Number of participants with the composite of cardiac death, valve thrombosis, valve-related thromboembolic event, major bleeding, and clinically-relevant non-major bleeding	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event	1 year
Number of Participants With the composite event of major bleeding and clinically-relevant non-major bleeding	1 year	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.
Number of Participants With all cause 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 myocardial infarction	1 year
Number of Participants With major bleeding	1 year	BARC (Bleeding Academic Research Consortium) 3 or 5
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 the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event	1 year
Number of Participants With Clinically-relevant non-major bleeding	1 year	BARC (Bleeding Academic Research Consortium) 2
Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event	1 year
Number of Participants With cardiovascular death	1 year
Number of Participants With valve-related thromboembolic	1 year
Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event	1 year
The change of echocardiographic parameter	1 year	Integral ratio at baseline and 1 year follow-up : effective orifice area(EOA)

Trial Locations

Locations (11)

Dong-A University Hospital; 🇰🇷 Busan, Korea, Republic of

GangNeung Asan Hospital; 🇰🇷 Gangneung, Korea, Republic of

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Buchen Sejong Hospital; 🇰🇷 Bucheon, Korea, Republic of

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of