Anticoagulant Versus Dual Antiplatelet Therapy for Preventing Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement (ADAPT-TAVR)

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

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).

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: NOAC; Drug: DAPT

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Korea, Republic of
  • Seongnam, Korea, Republic of
    • Bundang CHA Hospital
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of, 138-736
      • Asan Medical Center
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Cheng Hsin General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duk-Woo Park, MD
• Collaborators: CardioVascular Research Foundation, Korea; Daiichi Sankyo Korea Co., Ltd.
• Investigators: Principal Investigator: Seung-jung Park, MD, Cardiology, Asan Medical Center Heart Institute

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): October 26, 2021
• Study Completion (Actual): November 5, 2021

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: edoxaban; dual antiplatelet therapy; cerebral embolization; leaflet thrombosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Thrombosis
• Other Study ID Numbers: AMCCV 2017-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No