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

NCT03284827 | Completed Phase 4 DMC

• 1 other identifier: AMCCV 2017-08
• Study Type: interventional
• Target: 235
• Locations: 3 countries
• Sites: 5

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).

Conditions

Aortic Valve Stenosis

Keywords

edoxaban; dual antiplatelet therapy; cerebral embolization; leaflet thrombosis

Outcome Measures

Primary Outcomes (1)

• an incidence of leaflet thrombosis

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

  6-month

Secondary Outcomes (8)

• Death

  6-month

• Myocardial infarction

  6-month

• Stroke or transient ischemic attack

  6-month

• Bleeding event

  6-month

• The change of Echocardiographic parameter

  6-month

Study Arms (2)

NOAC

EXPERIMENTAL

60 mg once daily

Drug: NOAC

DAPT

ACTIVE COMPARATOR

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

Drug: DAPT

Interventions

NOAC DRUG

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

NOAC

DAPT DRUG

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

DAPT

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duk-Woo Park, MD: lead
• CardioVascular Research Foundation, Korea: collaborator
• Daiichi Sankyo Korea Co., Ltd.: collaborator

Study Sites (5)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Asan Medical Center

Seoul, Songpa-gu, 138-736, South Korea

Location

Bundang CHA Hospital

Seongnam, South Korea

Location

Cheng Hsin General Hospital

Taipei, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (4)

• Choi Y, Ahn JM, Kang DY, Kim HJ, Kim H, Lee J, Kim M, Park J, Kim KW, Koo HJ, Yang DH, Jung SC, Kim B, Anthony Wong YT, Simon Lam CC, Yin WH, Wei J, Lee YT, Kao HL, Lin MS, Ko TY, Kim WJ, Kang SH, Lee SA, Kim DH, Lee JH, Park SJ, Park DW; ADAPT-TAVR Investigators. Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2023 Dec 25;16(24):2967-2981. doi: 10.1016/j.jcin.2023.10.024.

  PMID: 38151311 DERIVED

• Jang MH, 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, Ko E, Lee SA, Kim DH, Kim H, Choi Y, Lee J, Park SJ, Park DW. Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement. Heart. 2023 Dec 20;110(2):140-147. doi: 10.1136/heartjnl-2023-322946.

  PMID: 37586823 DERIVED

• 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.

  PMID: 35373583 DERIVED

• 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.

  PMID: 33402409 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

N(4)-oleylcytosine arabinoside

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Seung-jung Park, MD

  Cardiology, Asan Medical Center Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 15, 2017
• Study Start: March 15, 2018
• Primary Completion: October 26, 2021
• Study Completion: November 5, 2021
• Last Updated: November 8, 2021

Record last verified: 2021-11

Locations

KR (2); HK (1); TW (2)