The CONFORM Pivotal Trial

Study Overview
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Brief Summary
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The CLAAS® device will be evaluated for safety and efficacy by establishing its performance is non-inferior to the commercially available WATCHMAN® and Amulet™ left atrial appendage closure devices in patients with non-valvular atrial fibrillation. Patients who are eligible for the trial will be randomized to receive either the CLAAS device or the WATCHMAN or Amulet™ devices and will be followed for 5 years after device implant.

Official Title
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An Evaluation of the Safety and Effectiveness of the Conformal CLAAS System for Left Atrial Appendage Occlusion

Conditions
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Atrial Fibrillation, Stroke

Intervention / Treatment
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* Device: CLAAS
* Device: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female aged ≥18 years Documented non-valvular AF (paroxysmal, persistent, or permanent) High risk of stroke or systemic embolism, defined as CHADS2 score of >2 or CHA2DS2-VASc score of ≥ 3 Has an appropriate rationale to seek a non-pharmacologic alternative to long-term oral anticoagulation Deemed by investigator to be suitable for short term oral anticoagulation therapy but deemed less favorable for long-term oral anticoagulation Deemed appropriate for LAA closure by the site investigator and a clinician not a part of the procedural team using a shared decision-making process in accordance with standard of care Able to comply with the protocol-specified medication regimen and follow-up evaluations The patient (or legally authorized representative, where allowed) has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate institutional review board (IRB)/Regional Ethics Board (REB) Exclusion Criteria: Pregnant or nursing patients and those who plan pregnancy in the period up to one year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure. Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., prior atrial septal defect [ASD] or patent foramen ovale [PFO], surgical repair or implanted closure device, or obliterated or ligated left atrial appendage) Atrial fibrillation that is defined by a single occurrence or that is transient or reversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures) A medical condition (other than atrial fibrillation) that mandates long-term oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or mechanical heart valve) History of bleeding diathesis or coagulopathy, or patients in whom antiplatelet and/or anticoagulant therapy is contraindicated Documented active infection 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 noted at the site of prior treatment Recent (within 30 days of index procedure) or planned (within 60 days post-procedure) cardiac or non-cardiac interventional or surgical procedure Recent (within 30 days of index procedure) stroke or transient ischemic attack Recent (within 30 days of index procedure) myocardial infarction Vascular access precluding delivery of implant with catheter-based system Severe heart failure (New York Heart Association Class IV) Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any mechanical valve implant Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation) Platelet count <75,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <3,000 cells/mm3 Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium) or that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial Unable to undergo general anesthesia Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years A condition which precludes adequate transesophageal echocardiographic assessment Echo exclusion criteria: Left atrial appendage anatomy which cannot accommodate either a commercially available control device or the CLAAS device per manufacturer IFU (e.g., the anatomy and sizing must be appropriate for both devices in order to be enrolled in the trial) Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus, as visualized by TEE prior to implant Left ventricular ejection fraction (LVEF) <30% Existing circumferential pericardial effusion >5 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology Atrial septal defect that warrants closure High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion >15 mm or length > 15 mm) or large shunt (early [within 3 beats] and/or substantial passage of bubbles, e.g., >20) Moderate or severe mitral valve stenosis (mitral valve area <1.5 cm2) Complex atheroma with mobile plaque of the descending aorta and/or aortic arch Evidence of cardiac tumor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLAAS<br>Transcatheter left atrial occluder | Device: CLAAS<br>* CLAAS<br>|
| Active Comparator: WATCHMAN / Amulet<br>Transcatheter left atrial occluder | Device: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder<br>* WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure-related complications, all-cause death, major bleeding | The primary safety endpoint is a composite of 1) major procedure-related complications including a) cardiac perforation, b) pericardial effusion requiring drainage, c) ischemic stroke, d) device embolization, and e) major vascular complications, or 2) major bleeding, or 3) all-cause death | 12 months | 
| Ischemic stroke and systemic embolism | The primary effectiveness endpoint is a composite of ischemic stroke and systemic embolism through 18 months. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Mortality | A secondary safety endpoint is all-cause mortality including cardiovascular through 18 months | 18 months | 
| Myocardial Infarction | A secondary safety endpoint is myocardial infarction evaluated through 7 days post-procedure | 7 days | 
| Neurologic Events | A secondary safety endpoint is neurologic events including stroke (ischemic and hemorrhagic) and TIA | 45 days | 
| Closure Success | A secondary performance and efficacy endpoint is closure success at 12 months based upon each of the following criteria: a) demonstration of peri-device flow </=5 mm, and b) demonstration of peri-device flow </=3 mm | 12 months |