iCLAS™ for Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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Clinical study to evaluate the safety and efficacy of the Adagio AF Cryoablation System (iCLAS™) in the ablation treatment of symptomatic, persistent atrial fibrillation (PsAF). Data will be used to support a pre-market application (PMA)

Detailed Description
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A staged pre-market, single-arm, clinical study designed to collect acute and long-term safety and efficacy data for the Adagio AF Cryoablation System (iCLAS™). Patient population will consist of symptomatic, persistent AF subjects completing a de novo ablation procedure. Enrollment will be 200 subjects at up to 20 global investigational sites. Subjects will receive an ablation with the ultra-low cryoablation device. Follow-up will include assessment at one, three, six, and twelve months.

Official Title
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iCLAS™ for Persistent Atrial Fibrillation

Conditions
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Persistent Atrial Fibrillation

Intervention / Treatment
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* Device: Adagio AF Cryoablation System (iCLAS™)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA IC1 Male or female between the ages of 18 and 80 years IC2 Currently scheduled for an ablation of symptomatic, PsAF defined as continuous AF that is sustained > 7-days and ≤ 12 months and documented by the following: a. Physician's note indicating continuous AF > 7 days and ≤ 12 months, AND b. One of the following: i. 24-hour Holter within 180 days of enrollment showing continuous AF, OR ii. Two electrocardiograms from any forms of rhythm monitoring (e.g., 12-lead ECGs or single lead ECGs) completed ≥ 7 days apart within 180 days of enrollment. IC3 Refractory to at least one class I or III AAD. (Refractory defined as not effective, not tolerated or not desired) IC4 Willingness, ability and commitment to participate in baseline and follow-up evaluations for the full length of the study IC5 Willingness and ability to give an informed consent EXCLUSION CRITERIA EC 1 In the opinion of the Investigator, any known contraindication to an atrial ablation, TEE, or anticoagulation. Including, but not limited to, the identification of any atrial thrombus or evidence of sepsis EC 2 Any duration of continuous AF lasting longer than 12-months EC 3 History of previous left atrial ablation or surgical treatment for AF/AFL/AT EC 4 Atrial fibrillation secondary to electrolyte imbalance, active thyroid disease, or any other reversible or non-cardiac cause EC 5 Structural heart disease as described below: Left ventricular ejection fraction (LVEF) < 40% based on most recent TTE Left atrial size > 55 mm (parasternal long axis view) documented within 6-months of screening NYHA Class III or IV heart failure documented within the previous 12-months An implanted pacemaker or ICD Previous cardiac surgery, ventriculotomy, or atriotomy (excluding atriotomy for CABG), Previous cardiac valvular surgical or percutaneous procedure, or prosthetic valve Interatrial baffle, closure device, patch, or PFO occluder Presence of a left atrial appendage occlusion device Presence of any pulmonary vein stenting devices Coronary artery bypass graft (CABG) or PTCA procedure within 6 months prior to procedure Unstable angina or ongoing myocardial ischemia Myocardial infarction within the previous six (6) months prior to procedure Moderate or severe mitral insufficiency or stenosis based on most recent TTE Atrial myxoma Significant congential anomaly EC 6 BMI > 40 BMI >35 and no prior sponsor approval into the study EC 7 Any previous history of cryoglobulinemia EC 8 History of blood clotting or bleeding disease EC 9 History of severe COPD requiring steroid use in the previous 12-months EC 10 History of severe sleep apnea (AHI > 30) not currently treated with a CPAP machine or other mechanical device EC 11 Any prior history of documented cerebral infarct including recent TIA (within one year) or systemic embolism (excluding a post-operative DVT) EC 12 Any prior history or current evidence of hemidiaphragmatic paralysis EC 13 Pregnant or lactating (current or anticipated during study follow-up) EC 14 Current enrollment in any other study protocol where testing or results from that study may interfere with the procedure or outcome measurements for this study EC 15 Any other condition that, in the judgment of the investigator, makes the patient a poor candidate for this procedure, the study or compliance with the protocol (includes vulnerable patient population, mental illness, addictive disease, terminal illness with a life expectancy of less than two years, extensive travel away from the research center, COVID-19 related concerns)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Symptomatic persistent atrial fibrillation that failed at least one class I or Class III AAD with no prior history of ablation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iCLAS Ablation<br>Ablation of the left and right atrium with the Adagio Medical iCLAS System | Device: Adagio AF Cryoablation System (iCLAS™)<br>* Endovascular ablation of the left and right atrium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of the proportion of subjects who are free from device/procedure related Major Adverse Events (MAEs) that occur following the cryoablation procedure. | MAEs include any of the following: Death Myocardial infarction Cardiac perforation/pericardial tamponade Cerebral infarct or systemic embolism Major bleeding requiring transfusion of blood products Mitral or tricuspid valve damage Symptomatic pulmonary vein stenosis Severe (≥ 70%) pulmonary vein stenosis Permanent phrenic nerve injury Access site complications requiring pharmacological or surgical intervention Atrio-esophageal fistula Pericarditis Heart block requiring a permanent pacemaker Vagal nerve injury with GI dysmotility Other serious adverse device effects (SADEs), including TIAs, adjudicated by an independent Clinical Events Committee (CEC) as probably or definitely related to the Adagio System | 12-months | 
| Analysis of the proportion of subjects receiving a single cryoablation who are free from any documented left atrial arrhythmia (AF/AFL/AT). | The primary effectiveness endpoint will be based on a centralized core lab interpretation of the recordings used in the endpoint analysis. | 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recording and analysis of all identified SAEs and SADEs through 12-months post-procedure. | Events will be sub-stratified based on time to event as follows: Early onset (procedure through 7-days post-ablation) Peri-procedure (> 7-days through 30-days post-ablation) Late onset (>30-days post ablation) | 12-months | 
| Analysis of the proportion of subjects with acute procedural (ablation) success | Documentation of pulmonary vein isolation and posterior wall isolation | 20-minutes following last ablation |