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

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

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

Study Overview

• Status: Recruiting
• Conditions: Thromboembolism; AORTIC VALVE DISEASES
• Intervention / Treatment: Drug: Rivaroxaban Oral Tablet; Drug: Vitamin K antagonist(warfarin)

• Study Type: Interventional
• Enrollment (Estimated): 1300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jung-hee Ham, RN; Phone Number: 82230104728; Email: cvcrc5@amc.seoul.kr

Study Locations

• South Korea
  • Bucheon-si, South Korea
    • Recruiting
    • Buchen Sejong Hospital
    • Contact: Hee-moon Lee, MD
    • Principal Investigator: Hee-moon Lee, MD
  • Bundang, South Korea
    • Not yet recruiting
    • Seoul National University Bundang Hospital
    • Contact: Hyung Gon Je, MD
    • Principal Investigator: Hyung Gon Je
  • Busan, South Korea
    • Recruiting
    • Dong-A University Hospital
    • Principal Investigator: Yong-rak Cho, MD
    • Contact: Yong-rak Cho, MD
  • Daegu, South Korea
    • Recruiting
    • Keimyung University Dongsan Hospital
    • Contact: Yoon-suk Kim, MD
    • Principal Investigator: Yoon-suk Kim, MD
  • Gangneung, South Korea
    • Recruiting
    • GangNeung Asan Hospital
    • Contact: Hanbit Park
    • Principal Investigator: Hanbit Park
  • Gwangju, South Korea
    • Recruiting
    • Chonnam National University Hospital
    • Contact: Kyo-sun Lee, MD
    • Principal Investigator: Kyo-sun Lee, MD
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
    • Contact: Dong-sub Jung, MD
    • Principal Investigator: Dong-sub Jung, MD
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
    • Contact: Jae-woong Choi, MD
    • Principal Investigator: Jae-woong Choi, MD
  • Seoul, South Korea, 138-736
    • Recruiting
    • Asan Medical Center
    • Principal Investigator: Joon-bum Kim, MD
    • Contact: Joon-Bum KIM, MD
  • Seoul, South Korea
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Ho-Sung Son, MD
    • Principal Investigator: Ho-Sung Son, MD
  • Suwon, South Korea
    • Recruiting
    • Ajou University Hospital
    • Contact: Soo Jin Park, MD
    • Principal Investigator: Soo Jin Park, MD
  • Suwon, South Korea
    • Not yet recruiting
    • St. Vincent's Hospital, Catholic University of Korea
    • Contact: Jin Won Shin, MD
    • Principal Investigator: Jin Won Shin, MD
  • Uijeongbu-si, South Korea
    • Not yet recruiting
    • Eulji University Uijeongbu Hospital
    • Contact: Joon Lee
    • Principal Investigator: Joon Lee
  • Ulsan, South Korea
    • Not yet recruiting
    • Ulsan University Hospital
    • Contact: Kwan-sik Kim, MD
    • Principal Investigator: Kwan-sik Kim, MD
  • Yangsan, South Korea
    • Recruiting
    • Pusan National University Yangsan Hospital
    • Contact: mi-hee Lim, MD
    • Principal Investigator: mi-hee Lim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Factor Xa inhibitor	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
Active Comparator: Vitamin K antagonist	Drug: Vitamin K antagonist(warfarin); For 12months, keep the international normalized ratio (INR) 1.7-3.0

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Joon Bum Kim
• Investigators: Principal Investigator: Jung-min Ahn, MD, drjmahn@gmail.com

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Aortic valve replacement; Mechanical valve
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Embolism and Thrombosis; Aortic Valve Disease; Thromboembolism; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Thiophenes; Rivaroxaban
• Other Study ID Numbers: AMCCV2020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No