Aspirin Monotherapy Versus Sequential Warfarin-Aspirin Therapy After TAVR in Patients With Pure Aortic Regurgitation (AWATAR)

Prospective, Multicenter, Randomized Controlled Trial Evaluating the Safety and Efficacy of Different Antithrombotic Therapy Strategies in Patients With Severe Aortic Regurgitation Undergoing Transcatheter Aortic Valve Replacement

This multicenter randomized controlled trial evaluates antithrombotic strategies post-TAVR in severe aortic regurgitation patients without long-term anticoagulation. Patients are randomized 1:1 to aspirin 75-100 mg daily for 12 months versus warfarin (INR 2-3) for 6 months followed by aspirin for 6 months. Primary hypothesis: aspirin is superior for bleeding and non-inferior for death/thrombosis. Primary endpoint is a composite of death, stroke, thrombosis, MI, embolism, and major bleeding at 1 year. Sample size: 1172. Follow-up: 30 days, 6 months, 12 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Regurgitation Disease
• Intervention / Treatment: Drug: Aspirin; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Estimated): 1172
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lai Wei, MD; Phone Number: +86-021-64041990; Email: Wei.lai@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Zhongshan Hospital, Fudan University
      • Contact: Lai Wei, MD; Phone Number: +86-021-64041990; Email: Wei.lai@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Patients with severe aortic regurgitation (AR) who achieve technical success after TAVR using devices specifically indicated for AR (per VARC-3 criteria).
• Trileaflet aortic valve anatomy.
• No long-term anticoagulation indication (including but not limited to: atrial fibrillation, mechanical mitral valve prosthesis, deep vein thrombosis, pulmonary embolism, left ventricular thrombus, pulmonary hypertension, or coagulation disorders) as confirmed by the investigator.
• Signed written informed consent and willingness to comply with randomization, study procedures, and follow-up.

Exclusion Criteria:

• Need for oral anticoagulation or dual antiplatelet therapy, or need for oral or intravenous strong CYP3A inhibitors that cannot be paused during the study period.
• Active pathological bleeding, subdural hematoma, or history of intracranial hemorrhage.
• Ischemic stroke within 30 days before TAVR.
• Acute myocardial infarction within 30 days.
• Severe hepatic insufficiency (cirrhosis, hepatic decompensation).
• Severe renal insufficiency (eGFR < 30 mL/min/1.73 m²) or need for renal replacement therapy.
• Stent implantation (including coronary, carotid, or peripheral arteries) within 12 months before TAVR, or planned stent implantation within 1 year after TAVR.
• Coronary artery bypass grafting (CABG) within 12 months before TAVR.
• Allergy, intolerance, or known resistance to aspirin, clopidogrel, or warfarin.
• Known coagulation disorders or bleeding diathesis (including but not limited to platelet count ≤50,000/mm³ at screening).
• Any contraindication to anticoagulation therapy.
• Prior aortic valve prosthesis (mechanical or bioprosthetic); mitral valve bioprosthesis replacement within 1 year before TAVR; or prior mitral mechanical valve replacement; or prior tricuspid valve replacement.
• Emergency TAVR with cardiogenic shock manifesting as low cardiac output, vasopressor or respiratory dependence, or mechanical hemodynamic support.
• Life expectancy <1 year (e.g., terminal malignancy).
• Participation in another investigational drug or device clinical study (patients who have completed the primary endpoint of the study and are currently in long-term follow-up are not excluded).
• Pregnancy or planned pregnancy, or use of estrogen or estrogen-like drugs (for women with suspected pregnancy, serum or urine human chorionic gonadotropin test must be negative before enrollment).
• Any other condition deemed by the investigator to be inappropriate for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin Monotherapy; Aspirin 75-100 mg orally once daily for 12 months	Drug: Aspirin; Aspirin 75-100 mg orally once daily
Active Comparator: Standard Therapy; Warfarin (INR 2-3) for 6 months, followed by Aspirin 75-100 mg once daily for 6 months	Drug: Aspirin; Aspirin 75-100 mg orally once daily; Drug: Warfarin; Warfarin orally with dose adjusted to maintain INR 2-3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Non-hierarchical Composite Endpoint	The primary endpoint is a non-hierarchical composite endpoint including all-cause death, stroke, prosthetic valve thrombosis, intracardiac thrombosis, myocardial infarction, deep vein thrombosis or pulmonary embolism, systemic embolism, and life-threatening, disabling, or major bleeding (VARC-3 definition).	12 months post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Composite Endpoint of All-Cause Death, Ischemic Stroke, Valve/Intracardiac Thrombosis, and Myocardial Infarction.	The first key secondary endpoint is composite of all-cause death, ischemic stroke, valve/intracardiac thrombosis, and myocardial infarction.	12 months post-procedure
Number of Participants Who Experienced Composite of Life-threatening, Disabling, or Major Bleeding (based on VARC-3 criteria Type 2-4)	Life-threatening or disabling bleeding Fatal bleeding OR Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in haemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 unitsa Major bleeding Overt bleeding either associated with a drop in the haemoglobin level of at least 3.0 g/dL or requiring transfusion of two or three units of whole blood/RBC AND Does not meet criteria of life-threatening or disabling bleeding	12 months post-procedure
Number of Participants Who Experience Composite of Cardiovascular Death, Major Bleeding, Stroke, and Myocardial Infarction		12 months post-procedure
Number of Participants Who Experience Clinical Efficacy Composite Endpoint	Composite endpoint requiring all of the following: freedom from all-cause death; freedom from all stroke; no hospitalization for valve-related or procedure-related reasons; and KCCQ overall score ≥45 with no more than a 10-point decrease from baseline.	12 months post-procedure
Number of Participants Who Experienced All-Cause Death		12 months post-procedure
Number of Participants Who Experience Clinically Significant Prosthetic Valve Thrombosis (VARC-3)	Based on VARC-3 criteria, clinically significant prosthetic valve thrombosis defined as clinical. sequelae of a thromboembolic event (e.g. stroke, TIA, retinal occlusion, other evidence of systemic thromboembolism) or worsening valve stenosis/ regurgitation (e.g. signs of heart failure, syncope) and Haemodynamic valve deterioration Stage 2 or 3 or Confirmatory imaging (CT evidence of HALT or TEE findings) In the absence of clinical sequelae, both Haemodynamic valve deterioration Stage 3 and Confirmatory imaging (CT evidence of HALT or TEE findings)	At 6 months and 12 months post-procedure
Number of Participants Who Experience Bioprosthetic Valve Deterioration Stage 3 by Echocardiography (VARC-3)	Bioprosthetic Valve Failure Stage 3 defined as increase in mean transvalvular gradient ≥20 mmHg resulting in mean gradient ≥30 mmHg with concomitant decrease in EOA ≥0.6 cm2 or ≥50% and/or decrease in Doppler velocity index ≥0.2 or ≥40% compared with echocardiographic assessment performed 1-3 months post-procedure, OR new occurrence, or increase of ≥2grades, of intraprosthetic AR resulting in severe AR	12 months post-procedure
Number of Participants Who Experience Hypo-Attenuated Leaflet Thickening (HALT) by CT		12 months post-procedure
Number of Participants Who Experienced Non-Procedure-Related Life-Threatening or Disabling Bleeding (VARC-3)		At 30 days and 12 months post-procedure
Number of Participants Who Experienced Major Bleeding	Based on VARC 2 criteria	At 30 days and 12 months post-procedure
Number of Participants Who Experienced Minor Bleeding	Based on VARC 2 criteria	At 30 days and 12 months post-procedure
Number of Participants Who Experienced Aortic Valve Re-Intervention		12 months post-procedure
Number of Participants Who Experienced Heart Failure Re-Hospitalization		12 months post-procedure
Number of Participants Who Experienced Infective Endocarditis	Infective Endocarditis defined as: Meeting at least one of the following criteria: Fulfills the Duke criteria for endocarditis; Intraoperative evidence of an abscess, pus, or vegetation secondary to infection, confirmed by histology or microbiology; Autopsy evidence of an abscess, pus, or vegetation.	12 months post-procedure
Number of Participants Who Experienced Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)	MACCE including cardiac death, aortic valve reintervention, stroke, myocardial infarction, heart failure readmission and life-threatening, disabling, or major bleeding.	At 30 days and 12 months post-procedure
Number of Participants Who Experienced NYHA Class Improvement		At 30 days and 12 months post-procedure

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Suzhou Jiecheng Medical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 27, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Coumarins; Benzopyrans; Salicylates; Hydroxybenzoates; 4-Hydroxycoumarins; Aspirin; Warfarin
• Other Study ID Numbers: KY2026134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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