Exploratory Observation of Two Short-term Regimens After LAA Occlusion by LAMax LAAC® Device for Subjects With Non-valvular Atrial Fibrillation

Study Overview
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Brief Summary
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This is a prospective, single-center, randomized, exploratory clinical observation to explore the overall benefit of short-term dual antiplatelet or novel oral anticoagulant regimens after left atrial appendage (LAA) occlusion by LAMax LAAC® occluder for subjects with non-valvular atrial fibrillation (AF), which will provide a basis for subsequent research on real-world safety and efficacy of LAA closure (LAAC).

Detailed Description
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Anticoagulation is necessary after transcatheter left atrial appendage closure (LAAC) and is important to prevent thrombosis and device-related thrombosis (DRT). Bleeding events and stroke should be reduced while reducing thrombosis. Based on the characteristics of the LAMax LAAC® device, experts recommend studying short-term medication regimens for patients with non-valvular atrial fibrillation after LAAC. This trial is a prospective, single-center, randomized, open-label and parallel design. It is estimated that 54 patients will take part in the study. Subjects with non-valvular atrial fibrillation undergo transcatheter LAAC using the LAMax LAAC® device, and then are randomly enrolled in observation group 1/observation group 2 of the medication regimen in a 1:1 ratio after LAAC. Observation group 1 (dual antiplatelet group, 27 subjects): 4 weeks post-LAAC (aspirin 100 mg + clopidogrel 75 mg); 4-24 weeks post-LAAC (aspirin/clopidogrel); recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant). Observation group 2 (novel oral anticoagulant group, 27 subjects): 4 weeks post-LAAC (conventional dose NOAC); 4-24 weeks post-LAAC (aspirin/clopidogrel); recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant).

Official Title
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A Prospective Exploratory Clinical Observation of Two Short-term Regimens (Dual Antiplatelet or Novel Oral Anticoagulant) for Subjects With Non-valvular Atrial Fibrillation After Left Atrial Appendage Occlusion by LAMax LAAC® Device

Conditions
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Non-valvular Atrial Fibrillation

Intervention / Treatment
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* Drug: Dual antiplatelet
* Drug: Novel oral anticoagulant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients ≥ 18 years old with non-valvular atrial fibrillation (AF); 2. Subjects with LAAC indications: according to the 2023 SCAI/HRS Expert Consensus Statement on Transcatheter Left Atrial Attachment Closure, transcatheter LAAC is suitable for non-valvular AF patients with high risk of thromboembolism but unsuitable for long-term use of oral anticoagulants (OACs), including the following situations: Have a much higher risk of having stroke (CHA2DS2-VASc score: male ≥ 2 points, female ≥ 3 points), Have OAC intolerance or a much higher risk of bleeding (such as HAS-BLED score ≥ 3 points), Have sufficient life expectancy (minimum>1 year) and expected to improve quality of life after LAAC; 3. Successful left atrial appendage occlusion with LAMax LAAC® device; 4. Patients and their families fully understand the purpose of the study, voluntarily participate in the study and sign the informed consent form. Exclusion Criteria: 1. Combined with other diseases except AF requiring long-term warfarin or other anticoagulant therapy; 2. Absolute contraindications for anticoagulation therapy or unacceptable bleeding risk with dual antiplatelet therapy; 3. Indications to dual antiplatelet therapy other than atrial fibrillation and/or left atrial appendage occlusion at the time of enrollment or predicted appearance of such indications within the duration of the trial (e.g. planned coronary revascularization); 4. Occluder dislocation, pericardial effusion (including new pericardial effusion and significantly increased pre-existing pericardial effusion) and other bleeding complications within 24 hours after LAAC; 5. Patients scheduled for catheter ablation after left atrial appendage electrical isolation and during the study; 6. Patients resistant to clopidogrel; 7. Patients requiring elective cardiac surgery; 8. Heart failure NYHA grade IV and not been corrected yet; 9. Patients with AF caused by rheumatic valvular heart disease, degenerative valvular heart disease, congenital valvular heart disease, severe mitral stenosis, aortic stenosis and other valvular diseases; 10. Initial atrial fibrillation, paroxysmal atrial fibrillation with a clear cause such as coronary artery bypass grafting (CABG) < 12 months, hyperthyroidism, etc. 11. Patients with acute myocardial infarction or unstable angina pectoris, or recent myocardial infarction < 12 months; 12. Patients with active bleeding, bleeding constitution or bleeding disorders, coagulation history and unhealed gastrointestinal ulcer; 13. Infective endocarditis, vegetation or other infections causing bacteremia, sepsis; 14. Female patients who are pregnant, lactating, or planning to become pregnant during this study; 15. Patients who have participated in other drug or device clinical trials and have not reached the endpoint; 16. Patients with renal insufficiency (endogenous creatinine clearance < 30ml/min) (using the standard Crockcroft-Gault formula) and/or advanced renal disease requiring dialysis; 17. Severe hepatic dysfunction (AST/ALT greater than 5 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal); 18. Patients considered unsuitable for this study by the investigator. 19. Left atrial appendage has been removed, post heart transplantation, post atrial septal repair, or post occluder implantation; 20. Post prosthetic heart valve replacement; 21. Allergic to or contraindication to metal nickel alloy, aspirin, clopidogrel, contrast agent, heparin and other anticoagulants, etc; 22. Patients who have placed other instruments in the cardiovascular cavity and are unable to place the LAA occluder; 23. LVEF（left ventricular ejection fraction, by Simpson method）<35%； 24. Clear thrombus is found in the heart before LAAC; 25. TEE examination: the maximal orifice diameter of LAA is less than 12 mm, or more than 36 mm; 26. Residual flow after LAAC >5mm； 27. Patent foramen ovale with high risk; 28. Mitral stenosis with a valve area <1.5cm2; 29. Left atrial diameter (antero-posterior diameter) > 65mm, or pericardial effusion more than a small amount, the depth of local effusion > 10 mm; 30. Contraindications to X-ray, or not suitable for TEE examination.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dual antiplatelet<br>Aspirin 100 mg + clopidogrel 75 mg for 4 weeks post-LAAC; followed by aspirin/clopidogrel for 4-24 weeks post-LAAC; recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant). | Drug: Dual antiplatelet<br>* Aspirin 100 mg + clopidogrel 75 mg for 4 weeks post-LAAC; followed by aspirin/clopidogrel for 4-24 weeks post-LAAC; recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant).<br>|
| Experimental: Novel oral anticoagulant<br>Conventional dose NOAC for 4 weeks post-LAAC; followed by aspirin/clopidogrel for 4-24 weeks post-LAAC; recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant). | Drug: Novel oral anticoagulant<br>* Conventional dose NOAC for 4 weeks post-LAAC; followed by aspirin/clopidogrel for 4-24 weeks post-LAAC; recommended long-term aspirin treatment after 24 weeks (clopidogrel can be used instead if aspirin is intolerant).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of device-related thrombosis | Incidence of device-related thrombosis (DRT) at the visit of 4 weeks post-LAAC documented by CTA and the visit of 24 weeks post-LAAC documented by transesophageal echocardiogram (TEE). | 24 weeks post-LAAC | 
| Incidence of stroke and transient ischemic attack | Incidence of stroke (classified as ischemic, hemorrhagic, or unspecified) and transient ischemic attack (TIA) before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding events | Incidence of bleeding events before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of systemic embolic events | Incidence of systemic embolic events before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of procedure-related complications | Incidence of procedure-related complications (including device embolization, significant pericardial effusion) before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of composite clinical endpoint events | Incidence of composite clinical endpoint events (including death, myocardial infarction, stroke, TIA) before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of all-cause mortality | Incidence of all-cause mortality (including cardiac death, non-cardiac death, and unexplained death) before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of myocardial infarction | Incidence of myocardial infarction before discharge or at 7 days, 4 weeks and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Incidence of major bleeding | Incidence of major bleeding (BARC type 3 and 5) before discharge or at 7 days, 4 weeks and 24 weeks post-LAAC. | 24 weeks post-LAAC | 
| Adverse events | Adverse events on the day of surgery, before discharge, or at 7 days, 4 weeks, and 24 weeks post-LAAC. | 24 weeks post-LAAC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Left Atrial Appendage Closure, Ischemic Stroke, Device-related Thrombosis