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

Aortic Valve Stenosis Clinical Trial

— ADAPT-TAVR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284827
• Other study ID #: AMCCV 2017-08
• Status: Completed
• Phase: Phase 4
• Start date: March 15, 2018
• Est. completion date: November 5, 2021

Study information

• Verified date: November 2021
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 235
• Est. completion date: November 5, 2021
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Thrombosis

Intervention

Drug:
• NOAC
edoxaban (60 mg once daily [OD]) for at least 6 months
• DAPT
clopidogrel (75 mg OD) plus acetylsalicylic acid (ASA, 75-100 mg OD) for at least 6 months

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong
Korea, Republic of	Bundang CHA Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul	Songpa-gu
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
Duk-Woo Park, MD	CardioVascular Research Foundation, Korea, Daiichi Sankyo Korea Co., Ltd.

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	an incidence of leaflet thrombosis	an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging	6-month
Secondary	Death	all-cause, cardiovascular, or non-cardiovascular mortality	6-month
Secondary	Myocardial infarction		6-month
Secondary	Stroke or transient ischemic attack	disabling or non-disabling	6-month
Secondary	Bleeding event	life-threatening or disabling, major bleeding, or minor bleeding according to VARC(The Valve Academic Research Consortium)-2 definition	6-month
Secondary	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
Secondary	New lesion volume on MRI scans		6-month
Secondary	The change of neurological and neurocognitive function	according to NeuroARC(Neuro Academic Research Consortium) definition	6-month
Secondary	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