Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation Compared to Medical Therapy
NCT ID: NCT03463317
Last Updated: 2025-12-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE4
912 participants
INTERVENTIONAL
2018-02-28
2024-11-30
Brief Summary
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Detailed Description
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A significant proportion of patients at high risk of stroke do not tolerate long-term anticoagulation due to various relative or absolute contraindications. As demonstrated in previous studies with non-vitamin K antagonist anticoagulants (NOAK), 20-25% of patients were unable to tolerate long-term anticoagulation therapy.
For this reason, additional therapeutic approaches for stroke prevention in patients with atrial fibrillation have been developed.
A promising approach is catheter-based closure of the left atrial appendage, because more than 90% of cardiac thrombi in patients with non-valvular atrial fibrillation are detected in the left atrial appendage. Recent registry studies show that the safety of LAA occluder implantation is promising. However, further scientific studies are required, in order to explore more benefits of the underlying method and eligible patients for implantation.
Study objectives:
The study goal is to determine the clinical benefit of percutaneous catheter-based left atrial appendage (LAA) closure in patients with non-valvular atrial fibrillation (NVAF) at high risk of stroke (CHA2DS2-VASc Score ≥2) as well as high risk of bleeding as compared to best medical care (including a \[non-vitamin K\] oral anticoagulant \[(N)OAC\] when eligible).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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LAA closure group
Left atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)
CE-mark approved LAA closure devices
LAA closure with post procedure treatment
Acetylsalicylic acid
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
Clopidogrel
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Dabigatran
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Rivaroxaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Apixaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Edoxaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Phenprocoumon
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Warfarin
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Interventions
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CE-mark approved LAA closure devices
LAA closure with post procedure treatment
Acetylsalicylic acid
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
Clopidogrel
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
Dabigatran
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Rivaroxaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Apixaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Edoxaban
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Phenprocoumon
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Warfarin
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Documented atrial fibrillation (paroxysmal, persistent, long-standing persistent or permanent)
* CHA2DS2VASc-Score ≥2
* High risk of bleeding under oral anticoagulation or contraindication for (N)OAC therapy, in particular patients with at least one of the following conditions:
* HAS-BLED-Score ≥3
* Prior intracranial/intraspinal bleed, intraocular bleed compromising vision (BARC: type 3c)
* Hemorrhagic/bleeding complication fulfilling BARC type 3a or 3b: gastrointestinal tract, genitourinary tract or respiratory tract bleeding, where the patient is considered to be at a persistently increased risk of bleeding, e.g. the cause of bleeding cannot be successfully eliminated
* Chronic kidney disease with eGFR 15-29 ml/min/1.73 m2
* Any recurrent bleeding making chronic anticoagulation not feasible
* Subject eligible for an LAA occluder device
* Age ≥18 years
* Willing and capable of providing informed consent, participating in all associated study activities
* negative SARS-CoV-2 PCR test (no longer than 48 hours prior to randomization in outpatients or not older than 14 days in continuously hospitalized patients without signs of COVID-19 infection) or negative SARS- CoV-2 rapid antigen test (no longer than 24 hours prior to randomization)
Exclusion Criteria
* Comorbidities other than AF requiring chronic (N)OAC therapy, e.g. mechanical heart valve prosthesis
* Symptomatic carotid disease (if not treated)
* Complex aortic atheroma with mobile plaque (Kronzon classification grade V)
* Heart transplant
* Active infection or symptoms suggestive of COVID-19 infection or active endocarditis or other infections resulting in bacteremia
* Cardiac tumor
* Severe liver failure (Child-Pugh class C or liver failure with coagulopathy)
* Severe renal failure (GFR \<15 ml/min/1.73m2 or current requirement for dialysis defined as current, regular renal replacement therapy performed at least weekly including hemodialysis and peritoneal dialysis within the last 30 days)
* Pregnancy or breastfeeding
* For female patients of reproductive potential: Unwilling to agree to use a highly effective method of contraception (Pearl index \<1) throughout the study period
* Subject with participation in another interventional clinical trial during this study or within 30 days before entry into this trial.
* Known terminating disease with life expectancy \<1 year (including those with end-stage heart failure)
* Subjects, who are committed to an institution due to binding official or court order
* Subject who is dependent on the Site, the Site Investigator, any sub- investigator, his/her representative and/or the sponsor
* Persons who are not proficient in the German language
* Unstable/not fully recompensated acute heart failure corresponding to NYHA class III and/or IV
* Subjects with known antiphospholipid syndrome
* Subjects with planned cardiac or non-cardiac surgery or intervention. (These subject can be included 30 days after such intervention / surgery.)
18 Years
ALL
No
Sponsors
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Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
OTHER
Atrial Fibrillation Network
OTHER
Stiftung Institut fuer Herzinfarktforschung
OTHER
Charite University, Berlin, Germany
OTHER
Responsible Party
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Ulf Landmesser
Prof. Dr.
Principal Investigators
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Ulf Landmesser, MD
Role: STUDY_CHAIR
Charite University, Berlin, Germany
Locations
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Charité Universitätsmedizin Berlin, Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin (CBF)
Berlin, , Germany
DRK-Kliniken Berlin Köpenick, Klinik für Innere Medizin - Schwerpunkt Kardiologie und Angiologie
Berlin, , Germany
Deutsches Herzzentrum der Charité, Klinik für Kardiologie, Angiologie und Intensivmedizin, Campus Virchow-Klinikum
Berlin, , Germany
Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Campus Virchow-Klinikum (CVK)
Berlin, , Germany
Charité Universitätsmedizin Berlin, Campus Charité Mitte, Med. Klinik für Kardiologie und Angiologie
Berlin, , Germany
Klinikum Brandenburg GmbH, Zentrum für Innere Medizin I
Brandenburg, , Germany
Gesundheit Nord gGmbH, Klinikum Links der Weser, Klinik für Kardiologie und Angiologie
Bremen, , Germany
Klinikum Coburg GmbH II. Med. Klinik für Innere Medizin und Kardiologie
Coburg, , Germany
Amper Kliniken AG, Helios Amper-Klinikum Dachau, Innere Medizin I - Kardiologie & Pneumologie
Dachau, , Germany
Städtisches Klinikum Dresden, II. Medizinische Klinik
Dresden, , Germany
Technische Universität Dresden, Herzzentrum Dresden, Universitätsklinik, Medizinische Klinik Kardiologie
Dresden, , Germany
Katholisches Krankenhaus "St. Johann Nepomuk", Klinik für Innere Medizin II - Kardiologie
Erfurt, , Germany
HELIOS Klinikum Erfurt GmbH, 3. Medizinische Klinik
Erfurt, , Germany
Universitätsklinikum Frankfurt, Medizinische Klinik III/ Kardiologie
Frankfurt, , Germany
UHZ Freiburg Bad Krozingen Klinik für Kardiologie und Angiologie II
Freiburg im Breisgau, , Germany
Universitätsmedizin Göttingen, Klinik für Kardiologie und Pneumologie
Göttingen, , Germany
Universität Greifswald, Klinik für Innere Medizin B - Kardiologie
Greifswald, , Germany
Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Innere Medizin III
Halle, , Germany
Asklepios Klinik Barmbek, I. Med. Abteilung - Kardiologie
Hamburg, , Germany
Asklepios Klinik St. Georg Hamburg, Abteilung für Kardiologie
Hamburg, , Germany
Cardiologicum Hamburg
Hamburg, , Germany
Universitätsklinikum Hamburg-Eppendorf, Universitäres Herzzentrum, Klinik für Allgemeine und Interventionelle Kardiologie
Hamburg, , Germany
Westküstenklinikum Heide Medizinische Klinik 2 - Kardiologie
Heide, , Germany
Universitätsklinikum Heidelberg, Medizinische Klinik für Kardiologie, Angiologie und Pneumologie
Heidelberg, , Germany
Oberhavel Kliniken, Klinik Hennigsdorf, Innere Medizin
Hennigsdorf, , Germany
Universitätsklinikum Jena, Klinik für Innere Medizin I - Kardiologie
Jena, , Germany
UKSH - Campus Kiel, Medizinische Klinik III - Kardiologie, Angiologie, Intensivmedizin
Kiel, , Germany
Herzzentrum Leipzig, Universitätsklinik für Kardiologie
Leipzig, , Germany
Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie
Leipzig, , Germany
UKSH - Universitäres Herzzentrum Lübeck, Medizinische Klinik II - Kardiologie, Angiologie, Intensivmedizin
Lübeck, , Germany
Universitätsmedizin Mainz, Kardiologie I - Zentrum für Kardiologie
Mainz, , Germany
Universitätsmedizin Mannheim, I. Medizinische Klinik - Kardiologie, Angiologie, Intensivmedizin
Mannheim, , Germany
Deutsches Herzzentrum München, Klinik an der TU München
München, , Germany
LMU Universität München, Medizinische Klinik und Poliklinik I
München, , Germany
Peter Osypka Herzzentrum München
München, , Germany
Städt. Klinikum München GmbH, Klinikum Neuperlach, Klinik für Kardiologie, Pneumologie, intern. Intensivmedizin
München, , Germany
Klinikum rechts der Isar, TU München, Klinik und Poliklinik für Innere Medizin I - Kardiologie
München, , Germany
Universitätsmedizin Rostock, Herzzentrum, Zentrum Innere Medizin - Abteilung für Kardiologie
Rostock, , Germany
Universitätsklinikum Tübingen, Medizinische Klinik, Abteilung III Kardiologie und Kreislauferkrankungen
Tübingen, , Germany
Universitätsklinik Ulm, Klinik für Innere Medizin II - Kardiologie
Ulm, , Germany
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik I
Würzburg, , Germany
Heinrich-Braun-Klinikum Zwickau, Klinik für Innere Medizin I - Kardiologie, Angiologie, Intern. Internsivmedizin
Zwickau, , Germany
Countries
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References
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Landmesser U, Skurk C, Kirchhof P, Lewalter T, Hartung J, Rroku A, Pieske B, Brachmann J, Akin I, Jacobshagen C, Meder B, Zeiher A, Anker SD, Thiele H, Blankenberg S, Massberg S, Schunkert H, Frey N, Joost A, Bergmann M, Haeusler KG, Endres M, Wegscheider K, Boldt LH, Eitel I. Catheter-based left atrial appendage CLOSURE in patients with atrial fibrillation at high risk of stroke and bleeding as compared to best medical therapy: Rationale and design of the prospective randomized CLOSURE-AF trial. Am Heart J. 2025 Sep 12;292:107273. doi: 10.1016/j.ahj.2025.09.005. Online ahead of print.
Related Links
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trial website
Other Identifiers
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CLOSURE-AF-DZHK16
Identifier Type: -
Identifier Source: org_study_id
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