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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Non-valvular Atrial Fibrillation
• Intervention / Treatment: Drug: Dual antiplatelet; Drug: Novel oral anticoagulant

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 Type: Interventional
• Enrollment (Estimated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Youqi Fan; Phone Number: +86-13867482684; Email: fanyouqi1228@126.com
• Study Contact Backup: Name: Jian'an Wang; Phone Number: +86-13805786328; Email: wangjianan111@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine at Zhejiang University
      • Contact: Youqi Fan, MD; Phone Number: +86-13867482684; Email: fanyouqi1228@126.com
      • Principal Investigator: Jian-an Wang, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. Have a much higher risk of having stroke (CHA2DS2-VASc score: male ≥ 2 points, female ≥ 3 points),
  2. Have OAC intolerance or a much higher risk of bleeding (such as HAS-BLED score ≥ 3 points),
  3. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: 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).
Experimental: 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).	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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Youqi Fan, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): November 16, 2024
• Study Completion (Estimated): May 16, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 9, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ischemic Stroke; Left Atrial Appendage Closure; Device-related Thrombosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anticoagulants
• Other Study ID Numbers: SAHZJU CT021

Drug and device information, study documents

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