Atrial Fibrillation with high risk of stroke and bleeding MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: ACETYLSALICYLIC ACID
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: ACETYLSALICYLIC ACID
Other descriptive name: ASA, ASS
Product Name: CLOPIDOGREL
Pharmaceutical For
Sponsors
Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) 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 ;Timepoint(s) of evaluation of this end point: Patients will be evaluated for the primary endpoint at follow up visits at 7 days*, 30 days*, 3, 6*, 12, 18*, 24, 36*, 48*, 60*, 72* and 84* months, EOS* (*phone visits). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Primary endpoint events per year - Combined endpoint: MACCE (stroke/systemic embolism/cardiovascular death/myocardial infarction) - Mortality (including all-cause death, cardiovascular death, non- cardiovascular death, peri-procedural death) - Major bleeding (BARC type 3-5) - Systemic embolism - Ischemic stroke - Hemorrhagic stroke - Transient ischemic attack (TIA; defined as neurological deficit of vascular origin lasting =24 hours without corresponding brain lesion) - Myocardial infarction - Hospitalization for bleeding or cardiovascular event - Changes in cognitive function assessed by MoCA (= Montreal Cognitive Assessment) - Changes in health-related quality of life (EQ-5D-5L) - Changes in modified Rankin Scale (mRS) Secondary safety endpoint(s): - Device-related complications until day 7 or discharge and total follow-up time - Device thrombus/fracture/erosion/infection/embolization - Pericardial effusion - Procedure related death - Technical and procedural success of device implantation (see also protocol chapter 4.2.4) - Peri-procedural outcomes at 7 days or discharge and 30 calendar days after implantation (see also protocol chapter 4.2.4) - Additionally, the total number of SAEs will be analyzed;Timepoint(s) of evaluation of this end point: Patients will be evaluated for the primary endpoint at follow up visits at 7 days*, 30 days*, 3, 6*, 12, 18*, 24, 36*, 48*, 60*, 72* and 84* months, EOS* (*phone visits). | — |
Countries
Germany
Contacts
Public ContactStudienzentrale
Klinik für Kardiologie, Angiologie und Intensivmedizin - Deutsches Herzzentrum der Charité - Campus Benjamin Franklin
Outcome results
None listed