Clinical trial NCT03284827: Anticoagulant Versus Dual Antiplatelet Therapy for Preventing Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aortic Valve Stenosis
Keywords: edoxaban
dual antiplatelet therapy
cerebral embolization
leaflet thrombosis
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: CardioVascular Research Foundation, Korea
name: Daiichi Sankyo Korea Co., Ltd.
First posted: 2017-09-15
Enrollment: 235
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. 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:

     1. correct positioning of a single prosthetic heart valve into the proper anatomical location AND
     2. 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
     3. 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.
2. Patients who voluntarily participated in the written agreement

Exclusion Criteria:

1. Any atrial fibrillation with an indication for chronic OAC.
2. An ongoing indication for OAC or any other indication for continued treatment with any OAC
3. Any ongoing indication for DAPT (recent acute coronary syndrome or PCI within 12 months)
4. Planned coronary or vascular intervention or major surgery
5. Clinically significant bleeding patients
6. 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
7. Clinically overt stroke within the last 3 months
8. Moderate and severe hepatic impairment, and any hepatic disease associated with coagulopathy
9. Severe renal impairment (CrCl by Cockcroft-Gault equation\<15 mL/min per 1.73 m2), chronic dialysis, or post-TAVR unresolved acute kidney injury
10. Terminal illness with life expectancy \<6 months
11. Hypersensitivity to the main component or constituents of Edoxaban
12. Severe hypertensive patient
13. Patient who received prosthetic heart valve replacement for which anticoagulant therapy is essential
14. Moderate to severe mitral stenosis
15. Pulmonary embolism requiring thrombolysis or pulmonary embolectomy
16. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period
17. 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
18. Genetic problem with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
19. History of hypersensitivity to Edoxaban, Aspirin or clopidogrel
20. Current or history of Aspirin- or NSAIDs-induced asthma
21. Hemophilia
22. Patients who are using Methotrexate at doses of 15mg or more per week
23. 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.

Primary outcomes:
measure: an incidence of leaflet thrombosis
timeFrame: 6-month
Secondary outcomes:
measure: Death
timeFrame: 6-month
measure: Myocardial infarction
timeFrame: 6-month
measure: Stroke or transient ischemic attack
timeFrame: 6-month
measure: Bleeding event
timeFrame: 6-month
measure: The change of Echocardiographic parameter
timeFrame: 6-month
measure: New lesion volume on MRI scans
timeFrame: 6-month
measure: The change of neurological and neurocognitive function
timeFrame: 6-month
measure: the number of new lesions on brain DW-MRI scans
timeFrame: 6-month
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
city: Seongnam
country: Korea, Republic of
facility: Bundang CHA Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Cardiology, Asan Medical Center Heart Institute
name: Seung-jung Park, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park DW, Ahn JM, Kang DY, Kim KW, Koo HJ, Yang DH, Jung SC, Kim B, Wong YTA, Lam CCS, Yin WH, Wei J, Lee YT, Kao HL, Lin MS, Ko TY, Kim WJ, Kang SH, Yun SC, Lee SA, Ko E, Park H, Kim DH, Kang JW, Lee JH, Park SJ; ADAPT-TAVR Investigators. Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial. Circulation. 2022 Aug 9;146(6):466-479. doi: 10.1161/CIRCULATIONAHA.122.059512. Epub 2022 Apr 4.
citation: Park H, Kang DY, Ahn JM, Kim KW, Wong AYT, Lam SCC, Yin WH, Wei J, Lee YT, Kao HL, Lin MS, Ko TY, Kim WJ, Kang SH, Ko E, Kim DH, Koo HJ, Yang DH, Kang JW, Jung SC, Lee JH, Yun SC, Park SJ, Park DW. Rationale and design of the ADAPT-TAVR trial: a randomised comparison of edoxaban and dual antiplatelet therapy for prevention of leaflet thrombosis and cerebral embolisation after transcatheter aortic valve replacement. BMJ Open. 2021 Jan 5;11(1):e042587. doi: 10.1136/bmjopen-2020-042587.