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Exploratory Observation of Regimens After LAA Occlusion by LAMax LAAC® Device for Subjects With High Risk of Bleeding

Primary Purpose

Non-valvular Atrial Fibrillation

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Dual antiplatelet
Novel oral anticoagulant
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Non-valvular Atrial Fibrillation focused on measuring Atrial Fibrillation, Left Atrial Appendage Closure, Ischemic Stroke, Device-related Thrombosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. Patients ≥ 18 years old with non-valvular atrial fibrillation (AF) and CHA2DS2-VASc ≥2; 2. Patients not suitable for long-term standardized anticoagulation, or stroke /embolic events still occurred on the basis of long-term standardized anticoagulation; 3. HAS-BLED ≥ 3; 4. Successful left atrial appendage occlusion with LAMax LAAC® device; 5. 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.

Sites / Locations

  • 2nd Affiliated Hospital, School of Medicine at Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dual antiplatelet

Novel oral anticoagulant

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

Incidence of bleeding events
Incidence of bleeding events before discharge or at 7 days, 4 weeks, and 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.
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.
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.
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.
Incidence of myocardial infarction
Incidence of myocardial infarction before discharge or at 7 days, 4 weeks and 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.
Adverse events
Adverse events on the day of surgery, before discharge, or at 7 days, 4 weeks, and 24 weeks post-LAAC.

Full Information

First Posted
February 27, 2023
Last Updated
February 27, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05761704
Brief Title
Exploratory Observation of Regimens After LAA Occlusion by LAMax LAAC® Device for Subjects With High Risk of Bleeding
Official Title
A Prospective Exploratory Clinical Observation of Anticoagulation and Antithrombotic Regimens After Left Atrial Appendage Occlusion by LAMax LAAC® Device for Subjects With Non-valvular Atrial Fibrillation at High Risk of Bleeding
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2023 (Actual)
Primary Completion Date
February 23, 2024 (Anticipated)
Study Completion Date
August 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a prospective, single-center, randomized, exploratory clinical observation to explore the overall benefit of optimized anticoagulation and antithrombotic regimens after left atrial appendage occlusion by LAMax LAAC® occluder for subjects with non-valvular atrial fibrillation (AF) at high risk of bleeding (HAS-BLED score ≥ 3).
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 medication regimens for patients with non-valvular atrial fibrillation at high risk of bleeding 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-valvular Atrial Fibrillation
Keywords
Atrial Fibrillation, Left Atrial Appendage Closure, Ischemic Stroke, Device-related Thrombosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dual antiplatelet
Arm Type
Experimental
Arm Description
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).
Arm Title
Novel oral anticoagulant
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Dual antiplatelet
Intervention Description
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 Type
Drug
Intervention Name(s)
Novel oral anticoagulant
Intervention Description
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).
Primary Outcome Measure Information:
Title
Incidence of device-related thrombosis
Description
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).
Time Frame
24 weeks post-LAAC
Title
Incidence of stroke and transient ischemic attack
Description
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.
Time Frame
24 weeks post-LAAC
Secondary Outcome Measure Information:
Title
Incidence of bleeding events
Description
Incidence of bleeding events before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC
Title
Incidence of systemic embolic events
Description
Incidence of systemic embolic events before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC
Title
Incidence of procedure-related complications
Description
Incidence of procedure-related complications (including device embolization, significant pericardial effusion) before discharge or at 7 days, 4 weeks, and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC
Title
Incidence of composite clinical endpoint events
Description
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.
Time Frame
24 weeks post-LAAC
Title
Incidence of all-cause mortality
Description
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.
Time Frame
24 weeks post-LAAC
Title
Incidence of myocardial infarction
Description
Incidence of myocardial infarction before discharge or at 7 days, 4 weeks and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC
Title
Incidence of major bleeding
Description
Incidence of major bleeding (BARC type 3 and 5) before discharge or at 7 days, 4 weeks and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC
Title
Adverse events
Description
Adverse events on the day of surgery, before discharge, or at 7 days, 4 weeks, and 24 weeks post-LAAC.
Time Frame
24 weeks post-LAAC

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Patients ≥ 18 years old with non-valvular atrial fibrillation (AF) and CHA2DS2-VASc ≥2; 2. Patients not suitable for long-term standardized anticoagulation, or stroke /embolic events still occurred on the basis of long-term standardized anticoagulation; 3. HAS-BLED ≥ 3; 4. Successful left atrial appendage occlusion with LAMax LAAC® device; 5. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Youqi Fan
Phone
+86-13867482684
Email
fanyouqi1228@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jian'an Wang
Phone
+86-13805786328
Email
wangjianan111@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Youqi Fan
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Affiliated Hospital, School of Medicine at Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Youqi Fan, MD
Phone
+86-13867482684
Email
fanyouqi1228@126.com
First Name & Middle Initial & Last Name & Degree
Jian-an Wang, MD,PhD

12. IPD Sharing Statement

Learn more about this trial

Exploratory Observation of Regimens After LAA Occlusion by LAMax LAAC® Device for Subjects With High Risk of Bleeding

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