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

Charite University, Berlin, Germany42 个研究点分布在 1 个国家目标入组 912 人开始时间: 2018年2月28日最近更新: 2025年12月12日

适应症

干预措施

试验速览

阶段: 4 期
状态: 已完成
发起方: Charite University, Berlin, Germany
入组人数: 912
试验地点: 42
主要终点: Primary endpoint (net clinical benefit)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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).

详细描述

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:

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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)

排除标准

•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
•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.)

研究组 & 干预措施

LAA closure group

Experimental

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)

干预措施: CE-mark approved LAA closure devices (Device)

LAA closure group

Experimental

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)

干预措施: Acetylsalicylic acid (Drug)

LAA closure group

Experimental

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)

干预措施: Clopidogrel (Drug)