Aortic Stenosis
Conditions
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.
Interventions
PROCEDURENo closure of left atrial appendage
aortic valve replacement with bioprosthesis according to indications in the current guidelines for the management of valvular heart disease.
PROCEDURESurgical 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.
Sponsors
Helsinki University Central Hospital
Kuopio University Hospital
St. Antonius Hospital
Landspitali University Hospital
University of Turku
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A composite of stroke, systemic embolism and cardiovascular mortality | 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| stroke/systemic embolism | 5 years | — |
| Surgery related bleeding (BARC 4) | 5 years | — |
| Stroke | 30 days postoperatively | 30D Post-op thromboembolism |
| A composite outcome of any of the following: stroke, systemic embolism and cardiovascular mortality | 30 days postoperatively | A composite outcome of stroke, systemic embolism and cardiovascular mortality |
| Any bleeding (BARC 1, 2 3a, b, c or 5) | 5 years | — |
Countries
Finland, Netherlands
Outcome results
None listed