Clinical trial NCT04258488: Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement
Official title: Randomized, Evaluation of Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: AORTIC VALVE DISEASES
Thromboembolism
Keywords: Aortic valve replacement
Mechanical valve
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2020-02-06
Enrollment: 1300
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with the composite of cardiac death, valve thrombosis, valve-related thromboembolic event, major bleeding, and clinically-relevant non-major bleeding
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants With all cause death
timeFrame: 1 year
measure: Number of Participants With cardiovascular death
timeFrame: 1 year
measure: Number of Participants With valve thrombosis confirmed by transthoracic echocardiography, transesophageal echocardiography, cine fluoroscopy, computed tomography, or autopsy (Valve Academic Research Consortium (VARC ) criteria)
timeFrame: 1 year
measure: Number of Participants With valve-related thromboembolic
timeFrame: 1 year
measure: Number of Participants With transient ischemic attack
timeFrame: 1 year
measure: Number of Participants With stroke
timeFrame: 1 year
measure: Number of Participants With systemic embolism
timeFrame: 1 year
measure: Number of Participants With myocardial infarction
timeFrame: 1 year
measure: Number of Participants With major bleeding
timeFrame: 1 year
measure: Number of Participants With Clinically-relevant non-major bleeding
timeFrame: 1 year
measure: Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event
timeFrame: 1 year
measure: Number of Participants With the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event
timeFrame: 1 year
measure: Number of Participants With the composite event of major bleeding and clinically-relevant non-major bleeding
timeFrame: 1 year
measure: Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event
timeFrame: 1 year
measure: Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event
timeFrame: 1 year
measure: The change of echocardiographic parameter
timeFrame: 1 year
measure: The change of echocardiographic parameter
timeFrame: 1 year
measure: The change of echocardiographic parameter
timeFrame: 1 year
measure: The change of echocardiographic parameter
timeFrame: 1 year
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Buchen Sejong Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Gangneung
country: Korea, Republic of
facility: GangNeung Asan Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: drjmahn@gmail.com
name: Jung-min Ahn, MD
role: PRINCIPAL_INVESTIGATOR
References: