Clinical trial NCT03463317: Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation Compared to Medical Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Anticoagulation
Left atrial appendage closure
Stroke
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Atrial Fibrillation Network
name: Stiftung Institut fuer Herzinfarktforschung
First posted: 2018-03-13
Enrollment: 912
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, event-driven, randomized controlled trial (Following 2nd blinded interim analysis: no longer event-driven).
Primary purpose: PREVENTION

Brief 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 \[non-vitamin K\] oral anticoagulant \[(N)OAC\] when eligible).

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).

Eligibility criteria: Key Inclusion Criteria:

* 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 (a-e):

  1. HAS-BLED-Score ≥ 3
  2. Prior intracranial/intraspinal bleed, intraocular bleed compromising vision (BARC: type 3c)
  3. 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
  4. Chronic kidney disease with eGFR 15-29 ml/min/1.73 m2
  5. 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

Key Exclusion Criteria:

* 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 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)
* 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
* Acute heart failure within the last 30 days
* Cardiac intervention within the last 30 days
* Subjects with planned cardiac or non-cardiac surgery or intervention. (These subject can be included 30 days after such intervention / surgery.)

Primary outcomes:
measure: Primary endpoint (net clinical benefit)
timeFrame: follow-up: 24 months
Secondary outcomes:
measure: Primary endpoint events per year
timeFrame: follow-up: 24 months
measure: Combined endpoint: MACCE
timeFrame: follow-up: 24 months
measure: Mortality
timeFrame: follow-up: 24 months
measure: Major bleeding
timeFrame: follow-up: 24 months
measure: Systemic embolism
timeFrame: follow-up: 24 months
measure: Ischemic/hemorrhagic stroke including transient ischemic attack
timeFrame: follow-up: 24 months
measure: Myocardial infarction
timeFrame: follow-up: 24 months
measure: Hospitalization for bleeding or cardiovascular event
timeFrame: follow-up: 24 months
measure: Changes in cognitive function
timeFrame: follow-up: 24 months
measure: Changes in health-related quality of life
timeFrame: follow-up: 24 months
measure: Device-related thrombus
timeFrame: follow-up: 24 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Vivantes Klinik Am Urban, Kardiologie
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, CBF, Kardiologie
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln, Kardiologie
city: Berlin
country: Germany
facility: DRK-Kliniken Berlin Köpenick, Klinik für Innere Medizin - Schwerpunkt Kardiologie und Angiologie
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, CVK, Kardiologie
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin, Innere Medizin - Kardiologie
city: Brandenburg
country: Germany
facility: Klinikum Brandenburg GmbH, Zentrum für Innere Medizin I
city: Bremen
country: Germany
facility: Gesundheit Nord gGmbH, Klinikum Links der Weser, Klinik für Kardiologie und Angiologie
city: Detmold
country: Germany
facility: Klinikum Lippe, Klinik für Kardiologie, Angiologie und Internistische Intensivmedizin
city: Erfurt
country: Germany
facility: Katholisches Krankenhaus "St. Johann Nepomuk", Klinik für Innere Medizin II - Kardiologie
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Medizinische Klinik II - Kardiologie und Angiologie
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus
city: Greifswald
country: Germany
facility: Universität Greifswald, Klinik für Innere Medizin B - Kardiologie
city: Hamburg
country: Germany
facility: Asklepios Klinik Barmbek, I. Med. Abteilung - Kardiologie
city: Herford
country: Germany
facility: Klinikum Herford, Med. Klinik III/ Kardiologie
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH, Klinik für Innere Medizin II - Kardiologie
city: Kiel
country: Germany
facility: UKSH - Campus Kiel, Medizinische Klinik III - Kardiologie, Angiologie, Intensivmedizin
city: Lübeck
country: Germany
facility: UKSH - Universitäres Herzzentrum Lübeck, Medizinische Klinik II - Kardiologie, Angiologie, Intensivmedizin
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz, Kardiologie I - Zentrum für Kardiologie
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, I. Medizinische Klinik - Kardiologie, Angiologie, Intensivmedizin
city: München
country: Germany
facility: Deutsches Herzzentrum München, Klinik an der TU München
city: München
country: Germany
facility: LMU Universität München, Medizinische Klinik und Poliklinik I
city: München
country: Germany
facility: Peter Osypka Herzzentrum München
city: München
country: Germany
facility: Städt. Klinikum München GmbH, Klinikum Neuperlach, Klinik für Kardiologie, Pneumologie, intern. Intensivmedizin
city: Ulm
country: Germany
facility: Universitätsklinik Ulm, Klinik für Innere Medizin II - Kardiologie
city: Zwickau
country: Germany
facility: Heinrich-Braun-Klinikum Zwickau, Klinik für Innere Medizin I - Kardiologie, Angiologie, Intern. Internsivmedizin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Ulf Landmesser, MD
role: STUDY_CHAIR
References: