amplatzer™ amulet™ laa occluder trial

Conditions: Stroke

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: 1. 18 years of age or older 2. documented paroxysmal, persistent, or permanent non-valvular atrial fibrillation (af) and the patient has not been diagnosed with rheumatic mitral valvular heart disease 3. at high risk of stroke or systemic embolism defined as chads2 score ≥ 2 or a cha2ds2-vasc score of ≥ 3 4. has an appropriate rationale to seek an alternative to warfarin or other anticoagulation medication 5. 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) 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) 7. able to comply with the required medication regimen post-device implant 8. able to understand and willing to provide written informed consent to participate in the trial 9. able and willing to return for required follow-up visits and examinations exclusion criteria: 1. requires long-term oral anticoagulation therapy for a condition other than atrial fibrillation 2. contraindicated for or allergic to aspirin, clopidogrel, or warfarin use 3. indicated for chronic p2y12 platelet therapy inhibitor 4. 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). 5. has undergone atrial septal defect (asd) repair or has an asd closure device present 6. has undergone patent foramen ovale (pfo) repair or has a pfo closure device implanted 7. implanted with a mechanical valve prosthesis 8. 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) 9. stroke or transient ischemic attack (tia) within 90 days prior to randomization or implant procedure (as applicable) 10. 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.) 11. myocardial infarction (mi) within 90 days prior to randomization 12. new york heart association class iv congestive heart failure 13. left ventricular ejection fraction (lvef) ≤30% 14. 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 15. reversible cause of af (i.e. secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures) 16. history of idiopathic or recurrent venous thromboembolism 17. left atrial appendage is obliterated or surgically ligated 18. thrombocytopenia or anemia requiring transfusions 19. 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) 20. actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial 21. subject is pregnant or pregnancy is planned during the course of the investigation 22. active endocarditis or other infection producing bacteremia 23. subject has had a transient case of af (i.e. never previously detected, provoked/induced by surgical or catheter manipulations, etc.) 24. subjects with severe renal failure (estimated glomerular filtration rate \<30ml/min/1.73m²) 25. subject whose life expectancy is less than 2 years 26. 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: 1. intracardiac thrombus visualized by echocardiographic imaging 2. existing circumferential pericardial effusion \>2mm 3. significant mitral valve stenosis (i.e. mitral valve area \<1.5 cm\^2) 4. 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) 5. complex atheroma with mobile plaque of the descending aorta and/or aortic arch 6. cardiac tumor 7. 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). 8. placement of the device would interfere with any intracardiac or intravascular structure

Keywords: non-valvular atrial fibrillation left atrial appendage