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

Phase 4

Completed

• Conditions: Aortic Valve Stenosis
• Interventions: Drug: NOAC; Drug: DAPT

• Registration Number: NCT03284827
• Lead Sponsor: Duk-Woo Park, MD

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-12
• Study First Submitted QC: 2017-09-13
• Study First Posted: 2017-09-15
• Study Start: 2018-03-15
• Primary Completion: 2021-10-26
• Status Verified: 2021-11
• Study Completion: 2021-11-05
• Last Update Submitted: 2021-11-05
• Last Update Posted: 2021-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 235

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NOAC	NOAC	60 mg once daily
DAPT	DAPT	clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD)

Primary Outcome Measures

Name	Time	Method
an incidence of leaflet thrombosis	6-month	an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Bundang CHA Hospital; 🇰🇷 Seongnam, Korea, Republic of

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Asan Medical Center; 🇰🇷 Seoul, Songpa-gu, Korea, Republic of

Cheng Hsin General Hospital; 🇨🇳 Taipei, Taiwan