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Atrial FibrillationPhase 4CLOSURE-AFNCT03463317

Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation Compared to Medical Therapy

A Phase 4 study testing CE-mark approved LAA closure devices, Acetylsalicylic acid and Clopidogrel in people with Atrial Fibrillation, run by Charite University, Berlin, Germany at 42 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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]… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
CE-mark approved LAA closure devices, Acetylsalicylic acid and Clopidogrel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
912 participants
Where
42 sitesGermany
Study dates
28 Feb 2018to 30 Nov 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • 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)
Show all 13Show fewer
  • 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)

Who cannot join

  • Absolute contraindication to acetylsalicylic acid
  • 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
Show all 19Show fewer
  • 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.)

Trial locations and contacts

42 sites in 1 country.

42 sites in 1 country

Germany42 sites

  • Charité Universitätsmedizin Berlin, Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Campus Benjamin Franklin (CBF)

    Berlin, 12203

  • DRK-Kliniken Berlin Köpenick, Klinik für Innere Medizin - Schwerpunkt Kardiologie und Angiologie

    Berlin, 12559

  • Deutsches Herzzentrum der Charité, Klinik für Kardiologie, Angiologie und Intensivmedizin, Campus Virchow-Klinikum

    Berlin, 13353

  • Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Campus Virchow-Klinikum (CVK)

    Berlin, 13353

  • Charité Universitätsmedizin Berlin, Campus Charité Mitte, Med. Klinik für Kardiologie und Angiologie

    Berlin

  • Klinikum Brandenburg GmbH, Zentrum für Innere Medizin I

    Brandenburg, 14770

  • Gesundheit Nord gGmbH, Klinikum Links der Weser, Klinik für Kardiologie und Angiologie

    Bremen, 28277

  • Klinikum Coburg GmbH II. Med. Klinik für Innere Medizin und Kardiologie

    Coburg

  • Amper Kliniken AG, Helios Amper-Klinikum Dachau, Innere Medizin I - Kardiologie & Pneumologie

    Dachau

  • Städtisches Klinikum Dresden, II. Medizinische Klinik

    Dresden

  • Technische Universität Dresden, Herzzentrum Dresden, Universitätsklinik, Medizinische Klinik Kardiologie

    Dresden

  • Katholisches Krankenhaus "St. Johann Nepomuk", Klinik für Innere Medizin II - Kardiologie

    Erfurt, 99097

  • HELIOS Klinikum Erfurt GmbH, 3. Medizinische Klinik

    Erfurt

  • Universitätsklinikum Frankfurt, Medizinische Klinik III/ Kardiologie

    Frankfurt

  • UHZ Freiburg Bad Krozingen Klinik für Kardiologie und Angiologie II

    Freiburg im Breisgau

  • Universitätsmedizin Göttingen, Klinik für Kardiologie und Pneumologie

    Göttingen

  • Universität Greifswald, Klinik für Innere Medizin B - Kardiologie

    Greifswald, 17475

  • Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Innere Medizin III

    Halle

  • Asklepios Klinik Barmbek, I. Med. Abteilung - Kardiologie

    Hamburg, 22291

  • Asklepios Klinik St. Georg Hamburg, Abteilung für Kardiologie

    Hamburg

  • Cardiologicum Hamburg

    Hamburg

  • Universitätsklinikum Hamburg-Eppendorf, Universitäres Herzzentrum, Klinik für Allgemeine und Interventionelle Kardiologie

    Hamburg

  • Westküstenklinikum Heide Medizinische Klinik 2 - Kardiologie

    Heide

  • Universitätsklinikum Heidelberg, Medizinische Klinik für Kardiologie, Angiologie und Pneumologie

    Heidelberg

  • Oberhavel Kliniken, Klinik Hennigsdorf, Innere Medizin

    Hennigsdorf

  • Universitätsklinikum Jena, Klinik für Innere Medizin I - Kardiologie

    Jena

  • UKSH - Campus Kiel, Medizinische Klinik III - Kardiologie, Angiologie, Intensivmedizin

    Kiel, 24105

  • Herzzentrum Leipzig, Universitätsklinik für Kardiologie

    Leipzig

  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie

    Leipzig

  • UKSH - Universitäres Herzzentrum Lübeck, Medizinische Klinik II - Kardiologie, Angiologie, Intensivmedizin

    Lübeck, 23538

  • Universitätsmedizin Mainz, Kardiologie I - Zentrum für Kardiologie

    Mainz, 55131

  • Universitätsmedizin Mannheim, I. Medizinische Klinik - Kardiologie, Angiologie, Intensivmedizin

    Mannheim, 68167

  • Deutsches Herzzentrum München, Klinik an der TU München

    München, 80636

  • LMU Universität München, Medizinische Klinik und Poliklinik I

    München, 81377

  • Peter Osypka Herzzentrum München

    München, 81379

  • Städt. Klinikum München GmbH, Klinikum Neuperlach, Klinik für Kardiologie, Pneumologie, intern. Intensivmedizin

    München, 81737

  • Klinikum rechts der Isar, TU München, Klinik und Poliklinik für Innere Medizin I - Kardiologie

    München

  • Universitätsmedizin Rostock, Herzzentrum, Zentrum Innere Medizin - Abteilung für Kardiologie

    Rostock

  • Universitätsklinikum Tübingen, Medizinische Klinik, Abteilung III Kardiologie und Kreislauferkrankungen

    Tübingen

  • Universitätsklinik Ulm, Klinik für Innere Medizin II - Kardiologie

    Ulm, 89081

  • Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik I

    Würzburg

  • Heinrich-Braun-Klinikum Zwickau, Klinik für Innere Medizin I - Kardiologie, Angiologie, Intern. Internsivmedizin

    Zwickau, 08060

Other trials in Germany

About this study

Official title: Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy: a Prospective Randomized Clinical Trial

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).

Read the detailed description

The individualized therapy with oral anticoagulants is considered to be an essential preventive therapy in patients with atrial fibrillation. The risk of stroke can be reduced by approximately 65%. However, long-term anticoagulation therapy also increases the risk of major bleeding.

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).

Being tested
CE-mark approved LAA closure devices, Acetylsalicylic acid, Clopidogrel, Dabigatran, Rivaroxaban
Keywords
Atrial Fibrillation, Anticoagulation, Left atrial appendage closure, Stroke
Medical subject headings
Atrial Fibrillation, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CE-mark approved LAA closure devicesDevice

    LAA closure with post procedure treatment

  • Acetylsalicylic acidDrug

    Also called ASS

    post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group

  • ClopidogrelDrug

    post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group

  • DabigatranDrug

    Also called Pradaxa®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

  • RivaroxabanDrug

    Also called Xarelto®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

  • ApixabanDrug

    Also called Eliquis®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

  • EdoxabanDrug

    Also called LIXIANA®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

  • PhenprocoumonDrug

    Also called Marcumar®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

  • WarfarinDrug

    Also called Coumadin®

    Patients allocated to the best medical care group receive either NOAC therapy or VKA

Study groups in NCT03463317
Study groupRoleWhat they receive
LAA closure groupExperimentalLeft atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)
Receives: Device: CE-mark approved LAA closure devices; Drug: Acetylsalicylic acid; Drug: Clopidogrel
Best medical care groupActive comparatorNo left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Receives: Drug: Dabigatran; Drug: Rivaroxaban; Drug: Apixaban; Drug: Edoxaban; Drug: Phenprocoumon; Drug: Warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary endpoint (net clinical benefit)

    Survival time free of the composite of:

    • Stroke (including ischemic or hemorrhagic stroke)
    • Systemic embolism
    • Major bleeding (BARC type 3-5)
    • Cardiovascular or unexplained death

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

Secondary outcomes (13)

  1. Primary endpoint events per year

    assessed by the number of primary endpoint events during the follow-up period.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  2. Combined endpoint: MACCE

    (stroke/systemic embolism/cardiovascular death/myocardial infarction)

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  3. Mortality

    (including all-cause death, cardiovascular death, non- cardiovascular death, peri-procedural death)

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  4. Major bleeding

    BARC type 3-5 (according to the BARC (Bleeding Academic Research Consortium) definition for bleeding).

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  5. Systemic embolism

    assessed by the rate of systemic embolism during the follow-up period.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  6. Ischemic stroke

    Stroke will be assessed according to 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials: A Report of the American College of Cardiology/AmericanHeart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol, 2015.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  7. Hemorrhagic stroke

    Stroke will be assessed according to 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials: A Report of the American College of Cardiology/AmericanHeart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol, 2015.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  8. Transient ischemic attack

    Defined as neurological deficit of vascular origin lasting ≤24 hours without corresponding brain lesion. TIA will be assessed according to 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials: A Report of the American College of Cardiology/AmericanHeart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol, 2015.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  9. Myocardial infarction

    Myocardial infarction will be assessed according to the third universal definition of myocardial infarction (Eur Heart J, 2012).

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  10. Hospitalization for bleeding or cardiovascular event

    Hospitalization for bleeding or cardiovascular event will be assessed according to 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials: A Report of the American College of Cardiology/AmericanHeart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol, 2015.

    Measured: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.

  11. Changes in cognitive function

    assessed by MoCA (= Montreal Cognitive Assessment). The MoCA will be used to assess the cognition of patients. Minimum score: 0 points, maximum score: 30 points.

    Measured: At day 0 and after 24 months.

  12. Changes in health-related quality of life

    assessed by EQ-5D-5L (German Version 1.0). The EQ-5D-5L consists of a 5-question multi-attribute questionnaire and a visual analogue self-rating scale. Minimum score: 0, maximum score: 100.

    Measured: At day 0 and after 6, and 12 months, twice a year until 24 months and once a year after 24 months of follow-up.

  13. Changes in modified Ranking Scale (mRS)

    Measured: At day 0, 1 day after implantation (device group only) and after 3, 12 and 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2018
  2. Study start28 Feb 2018
  3. Primary completion30 Nov 2024
  4. Study completion30 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, multicenter, event-driven, randomized controlled trial (Following 2nd blinded interim analysis: no longer event-driven).
Masking
None (open label)
Enrolment
912 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03463317
Sponsor's protocol ID
CLOSURE-AF-DZHK16
Acronym
CLOSURE-AF
Status last verified
Nov 2025
First submitted
16 Feb 2018
Last updated
12 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Claus F, Muller M, Fass E, Diesing J, Skurk C, Seppelt C, Meteva D, Rroku A, Eitel I, Boldt LH, Landmesser U, Wille E, Weinhold I. Health economic evaluation of left atrial appendage closure in patients with atrial fibrillation and at high risk for stroke and bleeding: a study protocol. Front Health Serv. 2026 Jul 1;6:1771683. doi: 10.3389/frhs.2026.1771683. eCollection 2026.

    PubMed 42459774

  • 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, von Bardeleben RS, Friede T, Placzek M, Suling A, Haeusler KG, Endres M, Wegscheider K, Boldt LH, Eitel I; CLOSURE-AF Trial Investigators. Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. N Engl J Med. 2026 Apr 2;394(13):1270-1280. doi: 10.1056/NEJMoa2513310. Epub 2026 Mar 18.

    PubMed 41849741

  • 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. 2026 Feb;292:107273. doi: 10.1016/j.ahj.2025.09.005. Epub 2025 Sep 12.

    PubMed 40946883

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing CE-mark approved LAA closure devices, Acetylsalicylic acid and Clopidogrel in people with Atrial Fibrillation, run by Charite University, Berlin, Germany at 42 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary endpoint (net clinical benefit) (time frame: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03463317, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.

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