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

• Sponsor: Joon Bum Kim (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04258488
• Collaborator: (none)
• Enrollment: 1,300
• Locations: 9
• Arms: 2
• Anticipated Duration (Months): 34.3
• Patients Per Site: 144.4
• Patients Per Site Per Month: 4.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
AORTIC VALVE DISEASES; Thromboembolism	Drug: Rivaroxaban Oral Tablet; Drug: Vitamin K antagonist(warfarin)	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 1300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Evaluation of Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement
• Actual Study Start Date: Feb 21, 2022
• Anticipated Primary Completion Date: Dec 31, 2023
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

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) 2.0-3.0

Outcome Measures

Primary Outcome Measures

1. 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

1. Number of Participants With all cause death [1 year]

2. Number of Participants With cardiovascular death [1 year]

3. 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]

4. Number of Participants With valve-related thromboembolic [1 year]

5. Number of Participants With transient ischemic attack [1 year]

6. Number of Participants With stroke [1 year]

7. Number of Participants With systemic embolism [1 year]

8. Number of Participants With myocardial infarction [1 year]

9. Number of Participants With major bleeding [1 year]

   BARC (Bleeding Academic Research Consortium) 3 or 5

10. Number of Participants With Clinically-relevant non-major bleeding [1 year]

    BARC (Bleeding Academic Research Consortium) 2

11. Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event [1 year]

12. Number of Participants With the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event [1 year]

13. 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.

14. Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event [1 year]

15. Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event [1 year]

16. The change of echocardiographic parameter [1 year]

    Integral ratio at baseline and 1 year follow-up : transaortic valve mean gradient

17. The change of echocardiographic parameter [1 year]

    Integral ratio at baseline and 1 year follow-up : transaortic valve peak gradient

18. The change of echocardiographic parameter [1 year]

    Integral ratio at baseline and 1 year follow-up : transaortic valve peak velocity

19. The change of echocardiographic parameter [1 year]

    Integral ratio at baseline and 1 year follow-up : effective orifice area(EOA)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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

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. Hepatic impairment, or severe (Child-Pugh C) or with 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

13. History of gastrointestinal ulcers or active ulcerations within the last 6 months

14. History of intracranial or intracerebral haemorrhage within the last 6 months

15. Spinal cord vascular abnormalities or intracerebral vascular abnormalities

16. History of the brain, spinal cord, or ophthalmic surgery within the last 6 months

17. History of the brain or spinal cord injury within the last 6 months

18. History of the brain or spinal cord injury or spinal tap, major regional anesthesia or, spinal anesthesia within the last 6 months

19. Esophageal varices

20. Arteriovenous malformation

21. Vascular aneurysms

22. Malignant tumor with a high risk of bleeding

23. Bleeding tendencies associated with overt bleeding of

24. gastrointestinal, genitourinary, respiratory tract or, colorectal cancer

25. cerebrovascular hemorrhage

26. aneurysms- cerebral, dissecting aorta

27. pericarditis and pericardial effusions

28. bacterial endocarditis

29. Hemodynamically unstable or pulmonary embolism required thrombolysis or embolectomy

30. 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

1. Uncontrolled moderate or severe hypertension

2. 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

3. Infective endocarditis

4. Hypersensitivity to the main component or constituents of Rivaroxaban or Vitamin K antagonist

5. Positive pregnancy test results (all pregnant women should undergo urinary human chorionic gonadotropin (hCG) testing within 7 days prior to screening and/or randomization) or during pregnancy or lactation

6. A genetic problem with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

7. The unsuitable condition to the protocol

8. Actively participating in another drug or device investigational study, which has not completed the primary endpoint follow-up period

9. Terminal illness with life expectancy <12 months

10. Vitamin K deficiency

11. Alcoholic or psychical disorder

12. Threatened abortion, eclampsia, or preeclampsia

13. Concomitant use with antiplatelet in patients with a history of stroke or transient ischemic attack for the treatment of acute coronary syndrome

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Buchen Sejong Hospital	Bucheon		Korea, Republic of
2	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of
3	Chonnam National University Hospital	Gwangju		Korea, Republic of
4	Asan Medical Center	Seoul		Korea, Republic of	138-736
5	Korea University Anam Hospital	Seoul		Korea, Republic of
6	Samsung Medical Center	Seoul		Korea, Republic of
7	Seoul National University Hospital	Seoul		Korea, Republic of
8	Ulsan University Hospital	Ulsan		Korea, Republic of
9	Pusan National University Yangsan Hospital	Yangsan		Korea, Republic of

Sponsors and Collaborators

• Joon Bum Kim

Investigators

• Principal Investigator: Jung-min Ahn, MD, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joon Bum Kim, Professor, Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT04258488
• Other Study ID Numbers: AMCCV2020-01
• First Posted: Feb 6, 2020
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Joon Bum Kim, Professor, Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center: Aortic valve replacement; Mechanical valve
• Additional relevant MeSH terms: Thromboembolism; Aortic Valve Disease; Vitamin K; Warfarin; Rivaroxaban

Study Results

No Results Posted as of Jul 22, 2022