Anticoagulant Versus Dual Antiplatelet Therapy for Preventing Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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This trial is to compare the efficacy of NOAC(Novel Oral Anticoagulants) with edoxaban vs. dual antiplatelet therapy (DAPT) for prevention of leaflet thrombosis (documented by cardiac CT imaging) and cerebral embolization (documented with brainDiffusion-weighted (DW) magnetic resonance (MR) imaging) in patients without an absolute indication for chronic oral anticoagulation (OAC) after successful transcatheter aortic valve replacement(TAVR).

Official Title
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a Multicenter, Randomized, Open-label, Active-treatment, Controlled Trial to Compare the Efficacy of NOAC With Edoxaban vs. Dual Antiplatelet Therapy (DAPT) for Prevention of Leaflet Thrombosis (Documented by Cardiac CT Imaging) and Cerebral Embolization (Documented With Brain DW-MRI Imaging) in Patients Without an Absolute Indication for Chronic OAC After Successful TAVR

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Drug: NOAC
* Drug: DAPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 19 years of age or older with successful TAVR procedure either native valve or valve-in-valve with any approved/marketed device A successful TAVR is defined as device success according to the VARC-2 criteria: correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no prosthesis- patient mismatch* and mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, no moderate or severe prosthetic valve regurgitation AND absence of periprocedural complications (any type of stroke, life-threatening bleeding, acute coronary artery obstruction requiring intervention, major vascular complication requiring intervention, unresolved acute valve thrombosis, or any requirement of a repeat procedure. Patients who voluntarily participated in the written agreement Exclusion Criteria: Any atrial fibrillation with an indication for chronic OAC. An ongoing indication for OAC or any other indication for continued treatment with any OAC Any ongoing indication for DAPT (recent acute coronary syndrome or PCI within 12 months) Planned coronary or vascular intervention or major surgery Clinically significant bleeding patients The risk of bleeding increased due to the following reasons at the time of TAVR procedure, i. history of gastrointestinal ulcers within 1 month ii. Malignant tumor with high risk of bleeding iii. Brain or spinal cord injury within 1 month iv. History of intracranial or intracerebral hemorrhage within 12 months v. Esophageal varices vi. Arteriovenous malformation vii. Vascular aneurysms viii. Spinal cord vascular abnormalities or intracerebral vascular abnormalities ix. Active bleeding x. Hemoglobin level <7.0 g/dL or platelet count ≤ 50,000 / mm3 xi. History of major surgery within 1 month Clinically overt stroke within the last 3 months Moderate and severe hepatic impairment, and any hepatic disease associated with coagulopathy Severe renal impairment (CrCl by Cockcroft-Gault equation<15 mL/min per 1.73 m2), chronic dialysis, or post-TAVR unresolved acute kidney injury Terminal illness with life expectancy <6 months Hypersensitivity to the main component or constituents of Edoxaban Severe hypertensive patient Patient who received prosthetic heart valve replacement for which anticoagulant therapy is essential Moderate to severe mitral stenosis Pulmonary embolism requiring thrombolysis or pulmonary embolectomy Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period Pregnancy test results are positive (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 Genetic problem with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption History of hypersensitivity to Edoxaban, Aspirin or clopidogrel Current or history of Aspirin- or NSAIDs-induced asthma Hemophilia Patients who are using Methotrexate at doses of 15mg or more per week Patients who have unsuitable condition to undergo Brain MRI(Magnetic resonance imaging) and/or Cardiac CT(computed tomography) (e.g., tremor from Parkinson's disease). This is at the discretion of investigators.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOAC<br>60 mg once daily | Drug: NOAC<br>* edoxaban (60 mg once daily [OD]) for at least 6 months<br>|
| Active Comparator: DAPT<br>clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD) | Drug: DAPT<br>* clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD) for at least 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| an incidence of leaflet thrombosis | an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging | 6-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | all-cause, cardiovascular, or non-cardiovascular mortality | 6-month | 
| Myocardial infarction |  | 6-month | 
| Stroke or transient ischemic attack | disabling or non-disabling | 6-month | 
| Bleeding event | life-threatening or disabling, major bleeding, or minor bleeding according to VARC(The Valve Academic Research Consortium)-2 definition | 6-month | 
| The change of Echocardiographic parameter | the mean transaortic valve pressure gradient and velocity time integral ratio at baseline and 6-month follow-up | 6-month | 
| New lesion volume on MRI scans |  | 6-month | 
| The change of neurological and neurocognitive function | according to NeuroARC(Neuro Academic Research Consortium) definition | 6-month | 
| the number of new lesions on brain DW-MRI scans | the number of new lesions on brain DW-MRI scans at 6 months relative to immediate post-TAVR | 6-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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edoxaban, dual antiplatelet therapy, cerebral embolization, leaflet thrombosis