Aortic Regurgitation Disease
Conditions
Brief summary
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
DRUGAspirin
Aspirin 75-100 mg orally once daily
DRUGWarfarin
Warfarin orally with dose adjusted to maintain INR 2-3
Sponsors
Shanghai Zhongshan Hospital
Suzhou Jiecheng Medical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Experimental Group: Aspirin 75-100 mg qd × 12 months Control (Standard) Group：Warfarin (INR 2-3) × 6 months, then aspirin 75-100 mg qd × 6 months
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Non-hierarchical Composite Endpoint | 12 months post-procedure | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Composite Endpoint of All-Cause Death, Ischemic Stroke, Valve/Intracardiac Thrombosis, and Myocardial Infarction. | 12 months post-procedure | The first key secondary endpoint is composite of all-cause death, ischemic stroke, valve/intracardiac thrombosis, and myocardial infarction. |
| Number of Participants Who Experienced Composite of Life-threatening, Disabling, or Major Bleeding (based on VARC-3 criteria Type 2-4) | 12 months post-procedure | 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 |
| 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 | 12 months post-procedure | 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. |
| Number of Participants Who Experienced All-Cause Death | 12 months post-procedure | — |
| Number of Participants Who Experience Clinically Significant Prosthetic Valve Thrombosis (VARC-3) | At 6 months and 12 months post-procedure | 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) |
| Number of Participants Who Experience Bioprosthetic Valve Deterioration Stage 3 by Echocardiography (VARC-3) | 12 months post-procedure | 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 |
| 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 | At 30 days and 12 months post-procedure | Based on VARC 2 criteria |
| Number of Participants Who Experienced Minor Bleeding | At 30 days and 12 months post-procedure | Based on VARC 2 criteria |
| 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 | 12 months post-procedure | 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. |
| Number of Participants Who Experienced Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) | At 30 days and 12 months post-procedure | MACCE including cardiac death, aortic valve reintervention, stroke, myocardial infarction, heart failure readmission and life-threatening, disabling, or major bleeding. |
| Number of Participants Who Experienced NYHA Class Improvement | At 30 days and 12 months post-procedure | — |
Countries
China
Contacts
CONTACTLai Wei, MD
Outcome results
None listed