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

Official title

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

Overview

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.

Interventions

• Drug Aspirin
  Aspirin 75-100 mg orally once daily
• Drug Warfarin
  Warfarin orally with dose adjusted to maintain INR 2-3

Primary outcome measures

• Number of Participants Who Experienced Non-hierarchical Composite Endpoint [Time frame: 12 months post-procedure]

Secondary outcome measures (12)

• Number of Participants Who Experienced Composite Endpoint of All-Cause Death, Ischemic Stroke, Valve/Intracardiac Thrombosis, and Myocardial Infarction. [Time frame: 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) [Time frame: 12 months post-procedure]
• Number of Participants Who Experience Composite of Cardiovascular Death, Major Bleeding, Stroke, and Myocardial Infarction [Time frame: 12 months post-procedure]
• Number of Participants Who Experience Clinical Efficacy Composite Endpoint [Time frame: 12 months post-procedure]
• Number of Participants Who Experienced All-Cause Death [Time frame: 12 months post-procedure]
• Number of Participants Who Experience Clinically Significant Prosthetic Valve Thrombosis (VARC-3) [Time frame: At 6 months and 12 months post-procedure]
• Number of Participants Who Experience Bioprosthetic Valve Deterioration Stage 3 by Echocardiography (VARC-3) [Time frame: 12 months post-procedure]
• Number of Participants Who Experience Hypo-Attenuated Leaflet Thickening (HALT) by CT [Time frame: 12 months post-procedure]
• Number of Participants Who Experienced Non-Procedure-Related Life-Threatening or Disabling Bleeding (VARC-3) [Time frame: At 30 days and 12 months post-procedure]
• Number of Participants Who Experienced Major Bleeding [Time frame: At 30 days and 12 months post-procedure]
• Number of Participants Who Experienced Minor Bleeding [Time frame: At 30 days and 12 months post-procedure]
• Number of Participants Who Experienced Aortic Valve Re-Intervention [Time frame: 12 months post-procedure]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT07677410 · KY2026134

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗