AMPLATZER™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,878
- 试验地点
- 227
- 主要终点
- Primary Safety Endpoint: Composite Endpoint Rate of Procedure-related Complications, or All-cause Death or Major Bleeding (Defined as Type 3 or Greater Based on the Bleeding Academic Research Consortium (BARC) Definition) (Non-inferiority Analysis)
研究概览
简要总结
The Amulet™ device will be evaluated for safety and efficacy by demonstrating its performance is non-inferior to the commercially available WATCHMAN® left atrial appendage closure device in patients with non-valvular atrial fibrillation. Patients who are eligible for the trial will be randomized to receive either the Amulet device or the WATCHMAN device and will be followed for 5 years after device implant.
详细描述
The Amulet IDE trial is a prospective, randomized, multi-center active control worldwide trial, designed to evaluate the safety and effectiveness of the AMPLATZER™ Amulet™ Left Atrial Appendage Occluder. Subjects will be randomized in a 1:1 ratio between the Amulet left atrial appendage (LAA) occlusion device (treatment) or a Boston Scientific WATCHMAN® LAA closure device (Control). The trial will be conducted at up to 150 sites worldwide. All enrolled subjects will follow the protocol-required tests and assessments at each scheduled follow-up visit.
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
- •18 years of age or older
- •Documented paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and the patient has not been diagnosed with rheumatic mitral valvular heart disease
- •At high risk of stroke or systemic embolism defined as CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3
- •Has an appropriate rationale to seek an alternative to warfarin or other anticoagulation medication
- •Deemed by investigator to be suitable for short term warfarin therapy but deemed unable to take long term oral anticoagulation, following the conclusion of shared decision making (see inclusion criteria #6)
- •Deemed suitable for LAA closure by a multidisciplinary team of medical professionals (including an independent non-interventional physician) involved in the formal and shared decision- making process, and by use of an evidence-based decision tool on oral anticoagulation (final determination must be documented in the subject's medical record)
- •Able to comply with the required medication regimen post-device implant
- •Able to understand and willing to provide written informed consent to participate in the trial
- •Able and willing to return for required follow-up visits and examinations
排除标准
- •Requires long-term oral anticoagulation therapy for a condition other than atrial fibrillation
- •Contraindicated for or allergic to aspirin, clopidogrel, or warfarin use
- •Indicated for chronic P2Y12 platelet therapy inhibitor
- •Is considered at high risk for general anesthesia, in the opinion of the investigator, and/or based on past adverse reaction(s) requiring medical intervention or which resulted in prolongation of hospital stay (criterion is only applicable where general anesthesia is planned for the study procedure).
- •Has undergone atrial septal defect (ASD) repair or has an ASD closure device present
- •Has undergone patent foramen ovale (PFO) repair or has a PFO closure device implanted
- •Implanted with a mechanical valve prosthesis
- •Has any of the customary contraindications for a percutaneous catheterization procedure (e.g. subject is too small to accommodate the transesophageal echocardiogram (TEE/TOE) probe or required catheters, or subject has active infection or bleeding disorder)
- •Stroke or transient ischemic attack (TIA) within 90 days prior to randomization or implant procedure (as applicable)
- •Underwent any cardiac or non-cardiac intervention or surgery within 30 days prior to randomization, or intervention or surgery is planned within 60 days after implant procedure (e.g. cardioversion, ablation, cataract surgery, etc.)
- •Myocardial infarction (MI) within 90 days prior to randomization
- •New York Heart Association Class IV Congestive Heart Failure
- •Left ventricular ejection Fraction (LVEF) ≤30%
- •Symptomatic carotid artery disease (defined as >50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is <50% stenosis
- •Reversible cause of AF (i.e. secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
- •History of idiopathic or recurrent venous thromboembolism
- •Left atrial appendage is obliterated or surgically ligated
- •Thrombocytopenia or anemia requiring transfusions
- •Hypersensitivity to any portion of the device material or individual components of either the Amulet or Boston Scientific LAA closure device (e.g. nickel allergy)
- •Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
- •Subject is pregnant or pregnancy is planned during the course of the investigation
- •Active endocarditis or other infection producing bacteremia
- •Subject has had a transient case of AF (i.e. never previously detected, provoked/induced by surgical or catheter manipulations, etc.)
- •Subjects with severe renal failure (estimated glomerular filtration rate <30ml/min/1.73m²)
- •Subject whose life expectancy is less than 2 years
- •Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical trial or to comply with follow up requirements, or impact the scientific soundness of the clinical trial results.
- •Echocardiographic Exclusion Criteria:
- •Intracardiac thrombus visualized by echocardiographic imaging
- •Existing circumferential pericardial effusion >2mm
- •Significant mitral valve stenosis (i.e. mitral valve area <1.5 cm^2)
- •High risk PFO, defined as an atrial septal aneurysm (excursion > 15mm or length ≥ 15mm; excursion defined as maximal protrusion of the atrial septal aneurysm [ASA] beyond the plane of the atrial septum) or large shunt (early, within 3 beats and/or substantial passage of bubbles i.e. ≥ 20)
- •Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
- •Cardiac tumor
- •LAA anatomy cannot accommodate either a Boston Scientific LAA closure device or Amulet device, as per manufacturer's Instructions for Use (IFU). (i.e. the LAA anatomy and sizing must be appropriate for both devices in order to be enrolled in the trial. This is applicable to all roll-in and randomized subjects).
- •Placement of the device would interfere with any intracardiac or intravascular structure
结局指标
主要结局
Primary Safety Endpoint: Composite Endpoint Rate of Procedure-related Complications, or All-cause Death or Major Bleeding (Defined as Type 3 or Greater Based on the Bleeding Academic Research Consortium (BARC) Definition) (Non-inferiority Analysis)
时间窗: At 12-months
Procedure related complications are adverse events adjudicated by the Clinical Events Committee (CEC), as procedure related and requiring either invasive surgical or percutaneous intervention. All-cause deaths (cardiovascular or non-cardiovascular) were assessed. Major Bleeding * Type 3a: * Any transfusion with overt bleeding * Overt bleeding+Hb drop of ≥ 3 to \< 5 g/dL (provided Hb drop is related to bleed) * Type 3b: * Overt bleeding+Hb drop ≥ 5 g/dL (provided Hb drop is related to bleed) * Cardiac tamponade * Bleeding requiring surgical intervention for (Watchman) * Bleeding requiring intravenous vasoactive drugs * Type 3c: * Intracranial hemorrhage including subdural hemorrhages * Subcategories confirmed by autopsy/imaging/lumbar puncture * Intraocular bleed compromising vision * Type 5a: Probably fatal bleeding * Type 5b: Definite fatal bleeding
Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis)
时间窗: At 45-days
Device closure (defined as residual jet around the device ≤ 5 mm) at the 45-day visit documented by transesophageal echocardiogram (TEE/TOE) defined by Doppler flow was assessed.
Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis)
时间窗: At 18-months
Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue. Systemic Embolism: Acute vascular insufficiency or occlusion of the extremities or any non-central nervous system (non-CNS) organ associated with clinical, imaging, surgical/autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation). When there is presence of prior peripheral artery disease, angiographic or surgical or autopsy evidence is required to show abrupt arterial occlusion.
次要结局
- Rate of Major Bleeding (Superiority Analysis)(At 18-months)
- Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism(At 18-months)
- Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis)(At 18-months)
- Superiority Test of Primary Safety Endpoint: Composite Endpoint Rate of Procedure-related Complications, or All-cause Death or Major Bleeding (Defined as Type 3 or Greater Based on the Bleeding Academic Research Consortium (BARC) Definition)(At 12-months)
- Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab(At 45-days)