Feasibility Study of a Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and function of the Aegis Sierra Ligation System in accessing and closing off the left atrial appendage (LAA) using a minimally invasive epicardial access approach. A minimum of 30 participants will be included in this study, which is being performed at a maximum of 8 centers in Canada and the United States. (A maximum of 15 participants at 4 US centers will be enrolled) Participants will be considered for this treatment if their doctor(s) have determined they have documented non-valvular atrial fibrillation and are at increased risk for developing a stroke.

Detailed Description
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Study Purpose: The objective of this early feasibility study is to assess the safety and function of the Aegis Sierra Ligation System (SLS) in ligating the left atrial appendage in patients with non-valvular atrial fibrillation and at risk for stroke. The results of this trial will be used to inform a larger pivotal trial that will allow for further health technology assessment and for Medical Device License applications. General Design: This is a prospective, single-arm, open-label, multi-center study. This study will screen patients with atrial fibrillation at risk for stroke. A minimum of 30 patients that meet all of the study's inclusion criteria, none of the exclusion criteria and consent to study participation will be enrolled. Patient accruement will take place at up to 8 North American centers (A maximum of 15 participants at 4 US centers will be enrolled). Each subject will undergo the following study visits: Screening, LAA ligation Procedure (Day 0) and Post-procedure, Hospital Discharge, Day 7, Day 30, Day 90, Day 180 and Day 365. The total duration of participation for subjects is anticipated to be 5 years post ligation procedure with the primary safety outcome assessed at the 30-day follow-up and the secondary endpoints assessed at Days 30, 180 and 365. Subjects will be also be contacted for an annual telephone follow-up evaluation from years 2 through 5 to assess for patient-reported long-term Major Adverse Events (MAE) and current health status.

Official Title
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A Single-arm, Open Label, Multi-Centre Feasibility Study of the Aegis Sierra Ligation System in Left Atrial Appendage Closure in Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Aegis Sierra Ligation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years Documented non-valvular atrial fibrillation Current CHA2DS2-VASc score of ≥2 Have an appropriate rationale to seek a non-pharmacologic alternative to oral anticoagulation (OAC) therapy Willing and able to provide written informed consent Willing and able to comply with study procedures and follow-up visits. Able to take antiplatelet therapy post ligation procedure Exclusion Criteria: Cardiogenic shock or hemodynamic instability Myocardial infarction in the past 3 months Cerebral embolism, stroke, or TIA in past 3 months Absence of a defined left atrial appendage on echocardiogram or CT scan Previous cardiac surgery involving opening of the pericardium History of pericarditis or pericardial tumor, a history of constrictive pericarditis or features which in the opinion of the investigator are suggestive of constrictive pericarditis History of significant chest trauma of the anterior chest Estimated life expectancy < 24 months Chemotherapy in the past 12 months Prior thoracic radiation therapy Chronic liver disease (greater than Child-Pugh Class A), chronic renal disease/insufficiency/failure (creatinine >3.0 mg/dL and/or renal replacement therapy at the time of screening), or chronic end stage pulmonary disease (FEV1 less than 30% predicted). Current use of long-term treatment with steroids. Does not include intermittent use of inhaled steroids for respiratory diseases. Contraindication to transesophageal echocardiography (TEE). Absolute contraindication to anticoagulation or antiplatelet therapy Congenital Heart Disease or intracardiac/intrapulmonary shunts Symptomatic or known significant carotid disease and/ or aortic arch atheroma Known thrombus in the LAA/LA or thrombus visualized by TEE within 48 hours before procedure Left ventricular ejection fraction (LVEF) below 30% Pregnant, breastfeeding or planning pregnancy within next 12 months Inappropriate appendage morphology (aberrant anatomy) as determined by imaging and assessed by Central Screening Committee Current NYHA Class IV heart failure symptoms Right ventricular dysfunction and /or pulmonary hypertension (>=50mmHG) Moderate or greater valve disease (i.e., MVA <1.5cm2, AVA <1.5cm2), history of rheumatic mitral stenosis, or mechanical valve prosthesis. Cardiac tumour Known hypersensitivity to nickel Patients in whom pericardial access will put the patient at risk (e.g. scoliosis, pectus excavatum, massive obesity with a BMI >40) as determined by clinical site Principal Investigator or Central Screening Committee. Current enrollment in an investigation or study of a cardiovascular device or investigational drug that would interfere with this study. Mental impairment or other conditions, which may not allow patient to understand the nature, significance and scope of the study. Any other criteria, which would make the patient unsuitable to participate in this study as determined by clinical site Principal Investigator or Central Screening Committee (e.g., uncontrolled drug and/or alcohol addiction, extreme frailty).

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aegis Sierra Ligation System<br>The Aegis Sierra Ligation System is a series of devices designed for epicardial ligation of the Left Atrial Appendage through a minimally invasive transcatheter approach. | Device: Aegis Sierra Ligation System<br>* The SLS is a series of devices designed for epicardial ligation of the left atrial appendage through a minimally invasive transcatheter approach.<br>* Other names: SLS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants free from the safety composite of device or procedure-related Major Adverse Events | Major Adverse Events : (defined as) All-cause death Stroke Systemic embolism Major or life-threatening bleeding (VARC-II definition), Injury to coronary arteries requiring intervention, Myocardial infarction (VARC-II definition), Unplanned operation or interventional procedure for device or procedure related complications (including drainage of pericardial effusion), Complications related to epicardial access | Day 30 from procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that experience a safety composite event | Components of the safety composites: All-cause death, stroke, trans-ischemic attack (TIA), systemic embolism | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience all-cause death | Number of participants that experience all-cause death at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience stroke | Number of participants that experience stroke at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience a trans-ischemic attack (TIA) | Number of participants that experience TIA at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience systemic embolism | Number of participants that experience systemic embolism at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience severe pericarditis | Number of participants that experience severe pericarditis at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience worsening heart failure | Worsening heart failure is defined as an increase in New York Heart Association (NYHA) Class ≥ category | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience a new occurrence of left atrial thrombus | Number of participants that experience a new occurrence of LAA thrombus at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that experience an access site wound infection requiring IV antibiotics | Number of participants that experience an access site wound infection requiring antibiotics at each designated time-point | Day 30, 6-months and 1-year from procedure | 
| Number of participants that achieve Technical Success | Technical success is defined as proper placement and positioning of the device includes the ability to access the pericardium, locate and grasp the LAA, and secure the ligating loop | Assessed at end of procedure | 
| Number of participants that achieve Procedural Success | Defined as Technical Success and no Major Adverse Events | Hospitalization period | 
| Number of participants that achieve a residual flow ≤ 5mm distal to the closure site as measured by transesophageal echo (TEE) | Number of participants that achieve a residual flow ≤ 5mm distal to the closure site as measured by transesophageal echo (TEE) at each time-point | Day 30, 6-months and 1-year from procedure | 
| The reported average change in B-type Natriuretic Peptide (BNP) | Reported in picomole/liter (pmol/L) | Change between baseline and 6-months from procedure | 
| The reported average change in the rating of atrial fibrillation burden as measured the University of Toronto Atrial Fibrillation Severity Scale (AFSS v. Sept 25, 2014) | Change in AFSS score between baseline to 6-months and 1-year from procedure will be reported | Change between baseline to 6-months and 1-year from procedure | 
| The reported average change in Health Related Quality of Life scoring as measured by the Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT v.1.0) | Change in AFEQT score between baseline, Day 30, 6-months and 1-year from procedure will be reported | Change between baseline to Day 30, 6-months, and 1-year from procedure | 
| The average change in patient reported pain as measured by the Numeric Rating Scale (NRS-11) pain scale. | Change in NRS pain score between baseline, hospital discharge,Day 7, and Day 30 from procedure will be reported | Change from baseline to hospital discharge, Day 7, and Day 30 from procedure |