Closing the left atrial appendage for patients with atrial fibrillation and stroke despite blood thinners

Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic StrokE Despite Anticoagulation Therapy

This study tests if closing a small part of the heart can help people with atrial fibrillation who have had a stroke while on blood thinners, to see if it lowers their chances of having another stroke.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 482 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Insel Gruppe AG, University Hospital Bern (Academic / other)
• Locations: 28 sites (Bruges and 27 other locations)
• Trial ID: NCT05976685 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of closing the left atrial appendage in patients with atrial fibrillation who have experienced an ischemic stroke despite being on anticoagulation therapy. The study aims to address the residual stroke risk that remains even with direct oral anticoagulants. By focusing on patients who have had a recent stroke, the trial seeks to determine if this intervention can reduce the likelihood of subsequent strokes. The approach combines observational data and interventional techniques to assess outcomes in a targeted patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a recent symptomatic ischemic stroke and a diagnosis of atrial fibrillation who are currently receiving anticoagulation therapy.

Not a fit: Patients who have contraindications to anticoagulation therapy or whose strokes are due to well-defined alternative causes may not benefit from this study.

Why it matters

Potential benefit: If successful, this intervention could significantly reduce the risk of recurrent strokes in patients with atrial fibrillation who are already on anticoagulation therapy.

How similar studies have performed: Previous studies have indicated that left atrial appendage occlusion may be beneficial for patients with atrial fibrillation, suggesting a promising avenue for this approach.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Written informed consent
* Permanent, persistent, or paroxysmal spontaneous AF previously known or diagnosed during the index hospitalization.
* Recent (≤3 months) symptomatic ischemic stroke.
* Active and ongoing anticoagulation therapy at stroke onset assessed based on medical history (i.e. any therapeutic oral anticoagulation therapy \[Vitamin K antagonist/DOAC according to prescription recommendations for AF; inadequate low-dose DOAC therapy allowed for inclusion\] not stopped/paused for \>48 hours due to any reason, i.e. medical intervention or non-adherence).
* Active or planned long-term therapy with DOAC

Exclusion Criteria:

* Contraindications to DOAC therapy
* Life expectancy \<1 year according to the opinion of the investigator
* Stroke due to: Ipsilateral intra/extracranial high-grade stenosis, Isolated lacunar stroke, Other well-defined stroke aetiologies (i.e., endocarditis, vasculitis, Reversible Cerebral Vasoconstriction Syndrome \[RCVS\], Posterior Reversible Encephalopathy Syndrome \[PRES\], cerebral sinus venous thrombosis)
* Previous persistent foramen ovale or atrial septum defect closure.
* Rheumatic heart disease
* Severe heart valve disease that requires treatment (severe aortic stenosis or regurgitation, severe mitral stenosis or regurgitation).
* Contraindications for TEE (relevant esophageal varices, esophageal stricture, history of esophageal cancer).
* Cardiac or non-cardiac surgical procedure within 30 days of randomization
* Enrolled in another investigation of a cardiovascular device or investigating secondary prevention therapy.
* Severely reduced Left Ventricular Ejection Fraction (LVEF) \<30%.
* Severe renal impairment as described in the summary of medicinal product characteristics for the chosen DOAC (e.g. rivaroxaban, apixaban and edoxaban creatinine clearance \<15 ml/min; dabigatran creatinine clearance \<30 ml/min).
* Hypertrophic cardiomyopathy
* Intracardiac tumor
* Ventricular thrombus
* Acute cardiac decompensation
* LAA is obliterated or surgically ligated
* Persistent proximal LAA thrombus despite 4 weeks of anticoagulation (if a proximal thrombus in the LAA is found, anticoagulation with vitamin K antagonist (INR 2.5-3.5) may be started, and if the thrombus disappears, the patient may be eligible for LAAO)
* Pregnancy or breastfeeding (pregnancy test in urine or blood to be performed at screening for women of childbearing potential)

Where this trial is running

Bruges and 27 other locations

• AZ Sint Jan Brugge — Bruges, Belgium (Recruiting)
• Brussels University Hospital — Brussels, Belgium (Recruiting)
• UCLouvain - Cliniques universitaires Saint-Luc — Brussels, Belgium (Recruiting)
• HUmani CHU Charleroi-Chimay — Charleroi, Belgium (Recruiting)
• Universitair Ziekenhuis (UZ) Leuven — Leuven, Belgium (Recruiting)
• UKSH, Campus Lübeck — Lübeck, Schleswig-Holstein, Germany (Recruiting)
• Charité-Universitätsmedizin Berlin — Berlin, Germany (Recruiting)
• Universitätsklinikum Bonn — Bonn, Germany (Recruiting)
• Universitätsmedizin Göttingen — Göttingen, Germany (Recruiting)
• Asklepios Klinik Altona — Hamburg, Germany (Recruiting)
• University Hospital Heidelberg — Heidelberg, Germany (Recruiting)
• Universitätsklinikum Leipzig — Leipzig, Germany (Recruiting)
• Universitätsmedizin Mannheim — Mannheim, Germany (Recruiting)
• Universitätsklinikum Tübingen — Tübingen, Germany (Recruiting)
• Christchurch Hospital — Christchurch, New Zealand (Recruiting)
• Hosp. Barcelona Santa Creu y Sant Pau — Barcelona, Spain (Recruiting)
• Vall d'Hebron University Hospital — Barcelona, Spain (Recruiting)
• Hosp. Clínic of Barcelona — Barcelona, Spain (Recruiting)
• Ente Ospedaliero Cantonale — Lugano, Canton Ticino, Switzerland (Recruiting)
• Centre Hospitalier Universitaire Vaudois — Lausanne, Vaude, Switzerland (Recruiting)
• University Hospital Basel — Basel, Switzerland (Recruiting)
• Inselspital, University Hospital Bern — Bern, Switzerland (Recruiting)
• Hôpitaux universitaires de Genève — Geneva, Switzerland (Not_yet_recruiting)
• Luzerner Kantonsspital — Lucerne, Switzerland (Not_yet_recruiting)
• Kantonsspital St. Gallen — Sankt Gallen, Switzerland (Recruiting)
• St Bartholomew's Hospital — London, United Kingdom (Recruiting)
• St Thomas' Hospital — London, United Kingdom (Recruiting)
• University Hospitals Sessex NHS Trust — Worthing, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Lorenz Räber, Prof., MD — Cardiovascular Center, Inselspital Bern
• Study coordinator: Lorenz Räber, Prof., MD, PhD

Conditions Ischemic Stroke; Atrial Fibrillation; Stroke; Direct oral anticoagulation; Left atrial appendage occlusion