Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery (LAA-CLOSURE)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Procedure: Surgical closure of left atrial appendage; Procedure: No closure of left atrial appendage

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 1040
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
  • Kuopio, Finland
    • Kuopio University Hospital
  • Turku, Finland, 20520
    • Turku University Hospital
• Netherlands
  • Utrecht, Netherlands
    • St Antonius Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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)
2. Age ≥18 years
3. No indication for long term anticoagulation at the time of enrollment.
4. Patients with CHADS-VASC score ≥2
5. Patient is willing to comply with specified follow-up evaluations
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BioAVR with surgical closure of LAA; 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; 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.
Placebo Comparator: BioAVR alone; 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; aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Turku
• Collaborators: Helsinki University Central Hospital; Kuopio University Hospital; St. Antonius Hospital; Landspitali University Hospital
• Investigators: Principal Investigator: Tuomas Kiviniemi, MD, PhD, Turku University Hospital, Turku, Finland

Publications and helpful links

Helpful Links

• Published trial protocol

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): April 30, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 16, 2014
• First Posted (Estimated): December 22, 2014

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: UTurku