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CompletedNCT03284827ADAPT-TAVRUpdated Nov 8, 2021

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

A Phase 4 interventional study of NOAC and DAPT in Aortic Valve Stenosis, sponsored by Duk-Woo Park, MD. Completed at 5 sites in 3 countries. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2021-11-08.

Sponsored by Duk-Woo Park, MD · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
235
Allocation
Randomized
Ages
19 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Aortic Valve Stenosis

Keywords

  • edoxaban
  • dual antiplatelet therapy
  • cerebral embolization
  • leaflet thrombosis
03

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
235 participants (actual)

Study arms

  • Experimental
    NOAC

    60 mg once daily

    Drug: NOAC

  • Active comparator
    DAPT

    clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD)

    Drug: DAPT

Interventions

  • DrugNOAC

    edoxaban (60 mg once daily \[OD\]) for at least 6 months

  • DrugDAPT

    clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD) for at least 6 months

05

What researchers measure

Primary outcomes

  1. an incidence of leaflet thrombosis

    an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging

    Time frame: 6-month

Secondary outcomes

  1. Death

    all-cause, cardiovascular, or non-cardiovascular mortality

    Time frame: 6-month

  2. Myocardial infarction

    Time frame: 6-month

  3. Stroke or transient ischemic attack

    disabling or non-disabling

    Time frame: 6-month

  4. Bleeding event

    life-threatening or disabling, major bleeding, or minor bleeding according to VARC(The Valve Academic Research Consortium)-2 definition

    Time frame: 6-month

  5. The change of Echocardiographic parameter

    the mean transaortic valve pressure gradient and velocity time integral ratio at baseline and 6-month follow-up

    Time frame: 6-month

  6. New lesion volume on MRI scans

    Time frame: 6-month

  7. The change of neurological and neurocognitive function

    according to NeuroARC(Neuro Academic Research Consortium) definition

    Time frame: 6-month

  8. 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

    Time frame: 6-month

06

Study locations

5 sites
  • Queen Mary Hospital
    Hong Kong, Hong Kong
  • Asan Medical Center
    Seoul, Songpa-gu 138-736, Korea, Republic of
  • Bundang CHA Hospital
    Seongnam, Korea, Republic of
  • Cheng Hsin General Hospital
    Taipei, Taiwan
  • National Taiwan University Hospital
    Taipei, Taiwan
07

References and documents

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. PubMed 35373583 ↗
  • 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. PubMed 33402409 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03284827
Lead sponsor
Duk-Woo Park, MD
Collaborators
CardioVascular Research Foundation, Korea, Daiichi Sankyo Korea Co., Ltd.
Responsible party
Duk-Woo Park, MD (Professor, Asan Medical Center) — Sponsor-investigator
First posted
Sep 15, 2017
Start date
Mar 15, 2018
Primary completion
Oct 26, 2021
Completion
Nov 5, 2021
Last update
Nov 8, 2021

Study contacts

Seung-jung Park, MD
principal investigator · Cardiology, Asan Medical Center Heart Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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