eft atrial appendage CLOSURE in patients with heart arrhythmia at high risk of stroke and bleeding compared to medical therapy.

Phase 1

Conditions: Atrial Fibrillation with high risk of stroke and bleeding
MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2017-000058-21-DE

Lead Sponsor: Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 970

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:
*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)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 700

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 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
-Subject with known antiphospholipid syndrome

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Study goal is to determine the clinical benefit of a strategy of percutaneous catheter-based left atrial appendage (LAA) closure in patients with NVAF at high risk of stroke (CHA2DS2-VASc Score =2) and bleeding as compared to best medical care (including a non-vitamin K antagonist oral anticoagulant [NOAC] if patient is eligible).;Secondary Objective: Not applicable.;Primary end point(s): Primary endpoint (net clinical benefit)<br>Survival time free of the composite of:<br>- Stroke (including ischemic or hemorrhagic stroke)<br>- Systemic embolism<br>- Major bleeding (BARC type 3-5)<br>- Cardiovascular or unexplained death<br>;Timepoint(s) of evaluation of this end point: Patients will be evaluated for the primary endpoint at follow up visits at<br>7 days, 30 days, 3, 6, 12, 18, 24, 36, 48, 60, 72 and 84* months, EOS* (*phone visits).

Secondary Outcome Measures