Title
Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation Compared to Medical Therapy
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
Phase
Phase 4Lead Sponsor
Humboldt UniversityStudy Type
InterventionalStatus
RecruitingIndication/Condition
Atrial FibrillationIntervention/Treatment
Acetylsalicylic acid Clopidogrel Dabigatran Rivaroxaban Apixaban Edoxaban Phenprocoumon Warfarin ...Study Participants
1512The 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).
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).
LAA closure with post procedure treatment
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
post procedure treatment according to the physicians (recommendation are made in the protocol); oral anticoagulation is not prescribed in this group
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Patients allocated to the best medical care group receive either NOAC therapy or VKA
Patients allocated to the best medical care group receive either NOAC therapy or VKA
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)
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
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): 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 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.)
