Clinical trial NCT02321137: Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery
Official title: A Randomized Prospective Multicenter Trial for Stroke Prevention by Surgical Occlusion of the Left Atrial Appendage in Patients Undergoing Aortic Bioprosthetic Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: University of Turku
Sponsor class: OTHER
Collaborators: name: Helsinki University Central Hospital
name: Kuopio University Hospital
name: St. Antonius Hospital
name: Landspitali University Hospital
First posted: 2014-12-22
Enrollment: 1040
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: A composite of stroke, systemic embolism and cardiovascular mortality
timeFrame: 5 years
Secondary outcomes:
measure: stroke/systemic embolism
timeFrame: 5 years
measure: cardiovascular mortality
timeFrame: 5 years
measure: Net adverse events (primary endpoint and major bleeding)
timeFrame: 5 years
measure: Hospitalization for decompensated heart failure
timeFrame: 5 years
measure: Major bleeding (BARC 3a, b, c or 5)
timeFrame: 5 years
measure: Any bleeding (BARC 1, 2 3a, b, c or 5)
timeFrame: 5 years
measure: Surgery related bleeding (BARC 4)
timeFrame: 5 years
measure: Stroke
timeFrame: 30 days postoperatively
measure: A composite outcome of any of the following: stroke, systemic embolism and cardiovascular mortality
timeFrame: 30 days postoperatively
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Utrecht
country: Netherlands
facility: St Antonius Hospital
Study officials:
affiliation: Turku University Hospital, Turku, Finland
name: Tuomas Kiviniemi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: