Randomized Comparison of Interventional Closure of the Left Atrial Appendage Using a LAA Closure Device Versus Oral Anticoagulation Therapy in Patients With Non-valvular Atrial Fibrillation and Status Post Intracranial Bleeding.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 530
- 试验地点
- 72
- 主要终点
- Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
研究概览
简要总结
Atrial fibrillation is the most common cardiac arrhythmia. In atrial fibrillation, there is a risk that clots can form in the heart, especially in the left atrium. If these clots come loose, there is a risk of stroke. To prevent strokes, patients with atrial fibrillation and status post ICB can be treated with anticoagulants. This medication therapy prevents blood clots from forming in the heart, but can also cause bleeding. Another therapy option is the occlusion of the left atrium. After closure of the left atrium, only a short anticoagulation therapy is necessary until the occluder has healed. The aim of the study is to compare these two treatment approaches. In this study only already approved drugs and occlusion systems will be used.
详细描述
Within the current trial, two novel strategies are tested in a randomized fashion in patients with atrial fibrillation and status post intracranial bleeding. Patients with ICH were usually excluded from the large NOAC trials and were also not representatively included in the large Watchman device trials. On the other hand, registries show that there is a significant proportion of patients with status post ICH that were implanted with a LAA closure device in clinical routine, and also there are those patients treated with NOAC due to their high stroke risk, despite the risk of recurrent ICH.
Both therapies, NOAC and LAA closure are effective in preventing stroke in patients with AF at high risk for stroke. Also, for both therapies there is evidence for prevention of bleedings, especially intracranial bleeding events.
Patients within the LAA closure group will have the chance after successful closure of the LAA to quit oral anticoagulation medication and therefore reduce their lifetime risk for bleeding and recurrent bleeding. Patients in the NOAC group are provided with an excellent protection against stroke and a significant reduced bleeding risk compared to Vitamin K antagonist therapy.
The trial will help to develop data and hopefully guidelines for management of patients with AF and status post intracranial bleedings. It may help to give physicians data to therapy patients post ICH adequately and help to reduce mortality rates in those patients.
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
- Single (Outcomes Assessor)
盲法说明
CEC blinded DSMB blinded
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
- •Status post intracranial bleeding >6 weeks
- •Favorable LAA anatomy
- •Subject eligible for a LAA occluder device
- •Age ≥18 years
排除标准
- •Comorbidities other than AF requiring chronic (N)OAC therapy, e.g. mechanical heart valve prosthesis, hereditary thrombophilia requiring livelong OAC - recurrent thrombosis
- •Symptomatic carotid disease (if not treated)
- •Thrombus in the left atrium or left atrial appendage
- •Active infection or active endocarditis or other infections resulting in bacteremia
- •Functional Impairment (modified ranking scale ≥4 )
- •Severe liver failure (Child-Pugh class C or liver failure with coagulopathy)
- •Pregnancy or breastfeeding
- •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
- •Subjects with planned cardiac or non-cardiac surgery or intervention. (These subjects can be included 30 days after intervention / surgery
研究组 & 干预措施
Left Atrial Appendage Occlusion
Percutaneous closure of the LAA by use of CE-mark approved LAA occlusion device Watchman / Watchman FLX
干预措施: Percutaneous closure of the LAA (Watchman / Watchman FLX) (Device)
Best Medical Therapy for Anticoagulation
Standard of care (according to current guidelines)
结局指标
主要结局
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
时间窗: up to 3 years after randomization
Cardiovascular or unexplained death Cardiovascular mortality: * Death due to proximate cardiac cause e.g. myocardial infarction, cardiac tamponade, worsening heart failure, or endocarditis * Death caused by non-coronary, non-CNS vascular conditions such as: pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm or other vascular disease * Death from vascular CNS causes from hemorrhagic and ischemic stroke * All procedure-related deaths including those related to a complication of the procedure or treatment for a complication of the procedure * Sudden or unwitnessed death defined as non-traumatic, unexpected fatal event occurring within one hour of the onset of symptoms in an apparently healthy subject. If death is not witness, the definition applies when the victim was in good health 24 hours before the event * Death of unknown cause
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
时间窗: up to 3 years after randomization
Bleeding (BARC type 2-5) - Type 2 Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional Type 3 1. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding 2. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents 3. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision Type 4 CABG-related bleeding within 48 hours Type 5 1. Probable fatal bleeding 2. Definite fatal bleeding (overt or autopsy or imaging confirmation)
次要结局
- Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year(up to 3 years after randomization)
- Hemorrhagic stroke(up to 3 years after randomization)
- Bleeding (BARC type 2-5)(up to 3 years after randomization)
- Ischemic stroke(up to 3 years after randomization)
- Combined endpoint: MACCE(up to 3 years after randomization)
- Mortality(up to 3 years after randomization)
- Systemic embolism(up to 3 years after randomization)
- Myocardial infarction(up to 3 years after randomization)
- Intracranial bleeding(up to 3 years after randomization)
- Hospitalization for bleeding or cardiovascular event(up to 3 years after randomization)
研究者
Sven Möbius-Winkler
Principal Investigator, Deputy Director Cardiology Departement
Jena University Hospital