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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Incidence of device-related thrombosis
Study Overview
Brief Summary
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
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients ≥ 18 years old with non-valvular atrial fibrillation (AF);
- •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;
- •Successful left atrial appendage occlusion with LAMax LAAC® device;
- •Patients and their families fully understand the purpose of the study, voluntarily participate in the study and sign the informed consent form.
Exclusion Criteria
- •Combined with other diseases except AF requiring long-term warfarin or other anticoagulant therapy;
- •Absolute contraindications for anticoagulation therapy or unacceptable bleeding risk with dual antiplatelet therapy;
- •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);
- •Occluder dislocation, pericardial effusion (including new pericardial effusion and significantly increased pre-existing pericardial effusion) and other bleeding complications within 24 hours after LAAC;
- •Patients scheduled for catheter ablation after left atrial appendage electrical isolation and during the study;
- •Patients resistant to clopidogrel;
- •Patients requiring elective cardiac surgery;
- •Heart failure NYHA grade IV and not been corrected yet;
- •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;
- •Initial atrial fibrillation, paroxysmal atrial fibrillation with a clear cause such as coronary artery bypass grafting (CABG) < 12 months, hyperthyroidism, etc.
- •Patients with acute myocardial infarction or unstable angina pectoris, or recent myocardial infarction < 12 months;
- •Patients with active bleeding, bleeding constitution or bleeding disorders, coagulation history and unhealed gastrointestinal ulcer;
- •Infective endocarditis, vegetation or other infections causing bacteremia, sepsis;
- •Female patients who are pregnant, lactating, or planning to become pregnant during this study;
- •Patients who have participated in other drug or device clinical trials and have not reached the endpoint;
- •Patients with renal insufficiency (endogenous creatinine clearance < 30ml/min) (using the standard Crockcroft-Gault formula) and/or advanced renal disease requiring dialysis;
- •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);
- •Patients considered unsuitable for this study by the investigator.
- •Left atrial appendage has been removed, post heart transplantation, post atrial septal repair, or post occluder implantation;
- •Post prosthetic heart valve replacement;
- •Allergic to or contraindication to metal nickel alloy, aspirin, clopidogrel, contrast agent, heparin and other anticoagulants, etc;
- •Patients who have placed other instruments in the cardiovascular cavity and are unable to place the LAA occluder;
- •LVEF（left ventricular ejection fraction, by Simpson method）<35%；
- •Clear thrombus is found in the heart before LAAC;
- •TEE examination: the maximal orifice diameter of LAA is less than 12 mm, or more than 36 mm;
- •Residual flow after LAAC >5mm；
- •Patent foramen ovale with high risk;
- •Mitral stenosis with a valve area <1.5cm2;
- •Left atrial diameter (antero-posterior diameter) > 65mm, or pericardial effusion more than a small amount, the depth of local effusion > 10 mm;
- •Contraindications to X-ray, or not suitable for TEE examination.
Arms & Interventions
Dual antiplatelet
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).
Intervention: Dual antiplatelet (Drug)
Novel oral anticoagulant
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).
Intervention: Novel oral anticoagulant (Drug)
Outcomes
Primary Outcomes
Incidence of device-related thrombosis
Time Frame: 24 weeks post-LAAC
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).
Incidence of stroke and transient ischemic attack
Time Frame: 24 weeks post-LAAC
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.
Secondary Outcomes
- Incidence of bleeding events(24 weeks post-LAAC)
- Incidence of procedure-related complications(24 weeks post-LAAC)
- Incidence of major bleeding(24 weeks post-LAAC)
- Incidence of all-cause mortality(24 weeks post-LAAC)
- Incidence of myocardial infarction(24 weeks post-LAAC)
- Incidence of composite clinical endpoint events(24 weeks post-LAAC)
- Adverse events(24 weeks post-LAAC)
- Incidence of systemic embolic events(24 weeks post-LAAC)
Investigators
Jian'an Wang,MD,PhD
President
Second Affiliated Hospital, School of Medicine, Zhejiang University