Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement (RENOVATE)
Primary Purpose
AORTIC VALVE DISEASES, Thromboembolism
Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Rivaroxaban Oral Tablet
Vitamin K antagonist(warfarin)
Sponsored by
About this trial
This is an interventional treatment trial for AORTIC VALVE DISEASES focused on measuring Aortic valve replacement, Mechanical valve
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
Sites / Locations
- Buchen Sejong Hospital
- Keimyung University Dongsan HospitalRecruiting
- Chonnam National University Hospital
- Asan Medical CenterRecruiting
- Korea University Anam Hospital
- Samsung Medical Center
- Seoul National University Hospital
- Ulsan University Hospital
- Pusan National University Yangsan HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Oral Factor Xa inhibitor
Vitamin K antagonist
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Participants With all cause death
Number of Participants With cardiovascular death
Number of Participants With valve thrombosis confirmed by transthoracic echocardiography, transesophageal echocardiography, cine fluoroscopy, computed tomography, or autopsy (Valve Academic Research Consortium (VARC ) criteria)
Number of Participants With valve-related thromboembolic
Number of Participants With transient ischemic attack
Number of Participants With stroke
Number of Participants With systemic embolism
Number of Participants With myocardial infarction
Number of Participants With major bleeding
BARC (Bleeding Academic Research Consortium) 3 or 5
Number of Participants With Clinically-relevant non-major bleeding
BARC (Bleeding Academic Research Consortium) 2
Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event
Number of Participants With the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event
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.
Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event
Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event
The change of echocardiographic parameter
Integral ratio at baseline and 1 year follow-up : transaortic valve mean gradient
The change of echocardiographic parameter
Integral ratio at baseline and 1 year follow-up : transaortic valve peak gradient
The change of echocardiographic parameter
Integral ratio at baseline and 1 year follow-up : transaortic valve peak velocity
The change of echocardiographic parameter
Integral ratio at baseline and 1 year follow-up : effective orifice area(EOA)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04258488
Brief Title
Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement
Acronym
RENOVATE
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jung-min Ahn
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AORTIC VALVE DISEASES, Thromboembolism
Keywords
Aortic valve replacement, Mechanical valve
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oral Factor Xa inhibitor
Arm Type
Experimental
Arm Title
Vitamin K antagonist
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban Oral Tablet
Intervention Description
For 12months, Rivaroxaban oral tablet 20mg once daily For renal disorder subjects_creatinine clearance 15-49 mL/min, 15mg once daily
Intervention Type
Drug
Intervention Name(s)
Vitamin K antagonist(warfarin)
Intervention Description
For 12months, keep the international normalized ratio (INR) 1.7-3.0
Primary Outcome Measure Information:
Title
Number of participants with the composite of cardiac death, valve thrombosis, valve-related thromboembolic event, major bleeding, and clinically-relevant non-major bleeding
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of Participants With all cause death
Time Frame
1 year
Title
Number of Participants With cardiovascular death
Time Frame
1 year
Title
Number of Participants With valve thrombosis confirmed by transthoracic echocardiography, transesophageal echocardiography, cine fluoroscopy, computed tomography, or autopsy (Valve Academic Research Consortium (VARC ) criteria)
Time Frame
1 year
Title
Number of Participants With valve-related thromboembolic
Time Frame
1 year
Title
Number of Participants With transient ischemic attack
Time Frame
1 year
Title
Number of Participants With stroke
Time Frame
1 year
Title
Number of Participants With systemic embolism
Time Frame
1 year
Title
Number of Participants With myocardial infarction
Time Frame
1 year
Title
Number of Participants With major bleeding
Description
BARC (Bleeding Academic Research Consortium) 3 or 5
Time Frame
1 year
Title
Number of Participants With Clinically-relevant non-major bleeding
Description
BARC (Bleeding Academic Research Consortium) 2
Time Frame
1 year
Title
Number of Participants With the composite of cardiac death, valve thrombosis and valve-related thromboembolic event
Time Frame
1 year
Title
Number of Participants With the composite of cardiac death, valve thrombosis, stroke, systemic embolism and myocardial infarction event
Time Frame
1 year
Title
Number of Participants With the composite event of major bleeding and clinically-relevant non-major bleeding
Description
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.
Time Frame
1 year
Title
Number of Participants With the composite of stroke, systemic embolism, transient ischemic attack and myocardial infarction event
Time Frame
1 year
Title
Number of Participants With the composite of all-cause death, stroke, systemic embolism, transient ischemic attack and myocardial infarction event
Time Frame
1 year
Title
The change of echocardiographic parameter
Description
Integral ratio at baseline and 1 year follow-up : transaortic valve mean gradient
Time Frame
1 year
Title
The change of echocardiographic parameter
Description
Integral ratio at baseline and 1 year follow-up : transaortic valve peak gradient
Time Frame
1 year
Title
The change of echocardiographic parameter
Description
Integral ratio at baseline and 1 year follow-up : transaortic valve peak velocity
Time Frame
1 year
Title
The change of echocardiographic parameter
Description
Integral ratio at baseline and 1 year follow-up : effective orifice area(EOA)
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jung-hee Ham, RN
Phone
82230104728
Email
cvcrc5@amc.seoul.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jung-min Ahn, MD
Organizational Affiliation
drjmahn@gmail.com
Official's Role
Principal Investigator
Facility Information:
Facility Name
Buchen Sejong Hospital
City
Bucheon
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hee-moon Lee, MD
First Name & Middle Initial & Last Name & Degree
Hee-moon Lee, MD
Facility Name
Keimyung University Dongsan Hospital
City
Daegu
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoon-suk Kim, MD
First Name & Middle Initial & Last Name & Degree
Yoon-suk Kim, MD
Facility Name
Chonnam National University Hospital
City
Gwangju
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyo-sun Lee, MD
First Name & Middle Initial & Last Name & Degree
Kyo-sun Lee, MD
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joon Bum Kim, MD
Phone
82-2-3010-5416
First Name & Middle Initial & Last Name & Degree
Joon-bum Kim, MD
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ho-Sung Son, MD
First Name & Middle Initial & Last Name & Degree
Ho-Sung Son, MD
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong-sub Jung, MD
First Name & Middle Initial & Last Name & Degree
Dong-sub Jung, MD
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jae-woong Choi, MD
First Name & Middle Initial & Last Name & Degree
Jae-woong Choi, MD
Facility Name
Ulsan University Hospital
City
Ulsan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kwan-sik Kim, MD
First Name & Middle Initial & Last Name & Degree
Kwan-sik Kim, MD
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyoung-gon Je, MD
First Name & Middle Initial & Last Name & Degree
Hyoung-gon Je, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Long-term Anticoagulation With Oral Factor Xa Inhibitor Versus Vitamin K Antagonist After Mechanical Aortic Valve Replacement
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