Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery

Study Overview
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Brief Summary
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The primary purpose of the LAA-CLOSURE trial is to assess the efficacy and safety of surgical closure of LAA in patients undergoing aortic valve replacement. This randomized, prospective, open-label international multicenter trial will enroll 1040 patients undergoing aortic valve replacement with CHA2DS2-VASC score ≥2 but without an indication for anticoagulation at the time of enrollment. Patients will be randomized in 1:1 fashion to standard therapy + surgical closure of LAA vs. standard therapy alone. The duration of the study is five years (plus additional 10 years).

Detailed Description
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Previous studies have concluded that ≥90% of AF related left atrial thrombi are located in the left atrial appendage (LAA). Surgical closure of LAA can be performed using ligation, stapler or other devices designed for this purpose during cardiac surgery. However, current evidence for surgical closure of LAA is scarce and no large scale randomized prospective clinical trials addressing this issue have been published. American College of Cardiology (ACC)/ American Heart Association (AHA) guidelines state that LAA exclusion should be considered in patients with recurrent and persistent AF who remain symptomatic with heart rate control and where antiarrhythmic medication is not tolerated or no longer effective. Current European Association of Cardiothoracic Surgery (EACTS) guidelines conclude that there is no proven benefit of surgical LAA exclusion in terms of stroke reduction or mortality benefit (level of evidence 2a B), and if exclusion is contemplated, devices designed for appendage exclusion should be used rather than a cut-and-sew or stapling technique. These guidelines are based on small poorly designed descriptive trials and only one small randomized trial. LAA-CLOSURE trial aims to assess efficacy and safety of prophylactic surgical closure of LAA in patients undergoing aortic valve replacement.

Official Title
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A Randomized Prospective Multicenter Trial for Stroke Prevention by Surgical Occlusion of the Left Atrial Appendage in Patients Undergoing Aortic Bioprosthetic Surgery

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Procedure: Surgical closure of left atrial appendage
* Procedure: No closure of left atrial appendage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing aortic valve replacement (+/- coronary bypass AND/OR mitral valve surgery) according to clinical indications (ESC guidelines for the management of valvular heart disease) Age ≥18 years No indication for long term anticoagulation at the time of enrollment. Patients with CHADS-VASC score ≥2 Patient is willing to comply with specified follow-up evaluations Patient or legally authorized representative has been informed of the nature of the study, agrees to its provisions and has been provided written informed consent, approved by the appropriate Medical Ethics committee or Institutional Review Board. Exclusion Criteria: Age < 18 years Expected survival < 1 year Chronic atrial fibrillation Indication for long term anticoagulation therapy before the index procedure Mechanical valve implantation previously or at the index procedure Any significant medical condition, which in the Investigator's opinion may interfere with the patient's optimal participation in the study.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BioAVR with surgical closure of LAA<br>Aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease including surgical closure of left atrial appendage | Procedure: Surgical closure of left atrial appendage<br>* aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease. The operation as well as the pre and post-operative care will be performed according to local surgical policies.<br>|
| Placebo Comparator: BioAVR alone<br>Aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease. | Procedure: No closure of left atrial appendage<br>* aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of stroke, systemic embolism and cardiovascular mortality |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stroke/systemic embolism |  | 5 years | 
| cardiovascular mortality |  | 5 years | 
| Net adverse events (primary endpoint and major bleeding) |  | 5 years | 
| Hospitalization for decompensated heart failure |  | 5 years | 
| Major bleeding (BARC 3a, b, c or 5) |  | 5 years | 
| Any bleeding (BARC 1, 2 3a, b, c or 5) |  | 5 years | 
| Surgery related bleeding (BARC 4) |  | 5 years | 
| Stroke | 30D Post-op thromboembolism | 30 days postoperatively | 
| A composite outcome of any of the following: stroke, systemic embolism and cardiovascular mortality | A composite outcome of stroke, systemic embolism and cardiovascular mortality | 30 days postoperatively |