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

Thromboembolism Clinical Trial

— RENOVATE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04258488
• Other study ID #: AMCCV2020-01
• Status: Recruiting
• Phase: Phase 4
• Start date: February 21, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2023
• Source: Asan Medical Center
• Contact: Jung-hee Ham, RN
• Phone: 82230104728
• Email: cvcrc5[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1300
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Disease
• AORTIC VALVE DISEASES
• Thromboembolism

Intervention

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
• Vitamin K antagonist(warfarin)
For 12months, keep the international normalized ratio (INR) 1.7-3.0

Locations

Country	Name	City	State
Korea, Republic of	Buchen Sejong Hospital	Bucheon
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	GangNeung Asan Hospital	Gangneung
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan

Sponsors (1)

Lead Sponsor	Collaborator
Jung-min Ahn

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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