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

Overview

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

Interventions

• Drug Rivaroxaban Oral Tablet
  For 12months, Rivaroxaban oral tablet 20mg once daily For renal disorder subjects\_creatinine clearance 15-49 mL/min, 15mg once daily
• Drug Vitamin K antagonist(warfarin)
  For 12months, keep the international normalized ratio (INR) 1.7-3.0

Primary outcome measures

• The event rate of the composite of cardiac death, valve thrombosis, valve-related thromboembolic event, major bleeding, and clinically-relevant non-major bleeding [Time frame: 1 year]

Secondary outcome measures (12)

• The event rate of all cause death [Time frame: 1 year]
• The event rate of cardiovascular death [Time frame: 1 year]
• The event rate of valve thrombosis confirmed by transthoracic echocardiography, transesophageal echocardiography, cine fluoroscopy, computed tomography, or autopsy (Valve Academic Research Consortium (VARC ) criteria) [Time frame: 1 year]
• The event rate of valve-related thromboembolic event [Time frame: 1 year]
• The event rate of transient ischemic attack [Time frame: 1 year]
• The event rate of stroke [Time frame: 1 year]
• The event rate of systemic embolism [Time frame: 1 year]
• The event rate of myocardial infarction [Time frame: 1 year]
• The event rate of major bleeding [Time frame: 1 year]
• The event rate of Clinically-relevant non-major bleeding [Time frame: 1 year]
• The event rate of the composite of cardiac death, valve thrombosis and valve-related thromboembolic event [Time frame: 1 year]
• The event rate of the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event [Time frame: 1 year]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 16 centers

• Buchen Sejong Hospital — Bucheon-si
• Dong-A University Hospital — Busan
• Keimyung University Dongsan Hospital — Daegu
• GangNeung Asan Hospital — Gangneung
• Chonnam National University Hospital — Gwangju
• Seoul National University Bundang Hospital — Seongnam
• Asan Medical Center — Seoul
• Korea University Anam Hospital — Seoul
• … and 8 more centers

Identifiers

NCT: NCT04258488 · AMCCV2020-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗