PersAFOne III: Feasibility Study of the FARAPULSE Pulsed Field Ablation System Plus - PersAF in the Treatment of Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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The objective of this safety and feasibility study is to assess whether the endocardial creation of electrically nonconductive lesions via PEF catheter ablation applied using the FARAPULSE Pulsed Field Ablation System Plus-PersAF is a feasible and safe treatment for PersAF and associated AFL

Detailed Description
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PersAFOne III study is a prospective, multi-center safety and feasibility study in subjects with persistent AF. Subjects will undergo percutaneous PEF ablation for pulmonary vein isolation as well as cavotricuspid isthmus interruption and other left atrial ablations at the investigator's discretion. Subjects will then be followed at 30 days, 60 ± 15 days, 6 months and 12 months for adverse events, recurrence of arrhythmia after a 90 day blanking period and other relevant outcome measures.

Official Title
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PersAFOne III: Feasibility Study of the FARAPULSE Pulsed Field Ablation System Plus - PersAF in the Treatment of Persistent Atrial Fibrillation

Conditions
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Persistent Atrial Fibrillation

Intervention / Treatment
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* Device: FARAPULSE™ Pulsed Field Ablation System Plus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study subjects are required to meet all the following inclusion criteria to participate in this study: Patients with documented drug-resistant symptomatic persistent AF meeting all three of the following criteria: Patient is refractory or intolerant to at least one Class I/III antiarrhythmic agent. ECG-documented first episode of persistent AF, lasting longer than 7 days but not longer than 365 days Holter within 90 days prior to the Enrollment Date demonstrating 24 hours of continuous AF Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment. Patient participation requirements: Lives locally Is willing and capable of providing Informed Consent to undergo study procedures Is willing to participate in all examinations and follow-up visits and tests associated with this clinical study - Exclusion Criteria: Subjects will be excluded from participating in this study if they meet any one of the following exclusion criteria: AF that is: Paroxysmal (longest AF episode < 7days) Longstanding (has persisted > 12 months or that does not respond to cardioversion if < 12 months) Secondary to electrolyte imbalance, thyroid disease, alcohol abuse or other reversible / non-cardiac causes Left atrial anteroposterior diameter ≥ 5.5 cm as documented by transthoracic echocardiography (TTE) or computed tomography (CT) Any of the following cardiac procedures, implants or conditions: Clinically significant arrhythmias other than AF, AFL or AT Hemodynamically significant valvular disease Prosthetic heart valve NYHA Class III or IV CHF Previous endocardial or epicardial ablation or surgery for AF Atrial or ventricular septal defect closure Atrial myxoma Left atrial appendage device or occlusion Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices Significant or symptomatic hypotension Bradycardia or chronotropic incompetence History of pericarditis History of rheumatic fever History of congenital heart disease with any residual anatomic or conduction abnormality Any of the following within 3 months prior toenrollment: Myocardial infarction Unstable angina Percutaneous coronary intervention Heart surgery (e.g. coronary artery bypass grafting, ventriculotomy, atriotomy) Heart failure hospitalization Stroke or TIA Clinically significant bleeding Pericarditis or pericardial effusion Left atrial thrombus History of blood clotting or bleeding abnormalities. Contraindication to, or unwillingness to use, systemic anticoagulation Contraindications to CT or MRI Sensitivity to contrast media not controlled by premedication Women of childbearing potential who are pregnant, lactating or not using birth control Medical conditions that would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or confound data or its interpretation, including but not limited to Body mass index (BMI) > 40 Solid organ or hematologic transplant, or currently being evaluated for an organ transplant Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or significant dyspnea Renal insufficiency with an estimated creatinine clearance <30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant Active malignancy or history of treated cancer within 24 months of enrollment Clinically significant gastrointestinal problems involving the esophagus, stomach and/or untreated acid reflux Clinically significant infection Predicted life expectancy less than one year Clinically significant psychological condition that in the investigator's opinion would prohibit the subject's ability to meet the protocol requirements Current or anticipated enrollment in any other clinical study Employment by FARAPULSE or the same hospital department or office of any investigator, or a family member of any of the preceding groups. Use of amiodarone after day of index ablation procedure. Patients will cease use of amiodarone on or before the date of the index ablation procedure. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: FARAPULSE™ Pulsed Field Ablation System Plus<br>Ablation using FARAPULSE™ Pulsed Field Ablation System Plus | Device: FARAPULSE™ Pulsed Field Ablation System Plus<br>* Ablation using FARAPULSE™ Pulsed Field Ablation System Plus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Safety Endpoint (CSE) defined as the incidence of the following early-onset and late-onset serious adverse events (SAEs) which are device- or procedure-related, as adjudicated by the CEDMC | Proportion of Intent to Treat subjects with one or more of the specified device or procedure related SAEs Endpoint(CSE) defined as the incidence of the following early-onset serious adverse events (SAEs) which are device- or procedure-related, as adjudicated by the Clinical Events and Data Monitoring Committee (CEDMC). Atrioesophageal fistula and PV stenosis components will be assessed for occurrence at any time during follow-up. Early onset (within 30 days of an Index or Remap Procedure) Death Myocardial infarction (MI) Persistent diaphragmatic paralysis Stroke or transient ischemic attack (TIA) Peripheral or organ thromboembolism Pericarditis Cardiac tamponade / perforation Vascular access complications requiring intervention Heart block Late onset (any time during follow-up through 12 months) Pulmonary vein (PV) stenosis (> 70% diameter reduction from baseline) Atrio-esophageal fistula | 30-Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Safety Endpoint assessed at 7 days | Proportion of Intent to Treat subjects with one or more of the specified device or procedure related SAEs Endpoint(CSE) defined as the incidence of the following early-onset serious adverse events (SAEs) which are device- or procedure-related, as adjudicated by the Clinical Events and Data Monitoring Committee (CEDMC). Atrioesophageal fistula and PV stenosis components will be assessed for occurrence at any time during follow-up. Early onset (within 30 days of an Index or Remap Procedure) Death Myocardial infarction (MI) Persistent diaphragmatic paralysis Stroke or transient ischemic attack (TIA) Peripheral or organ thromboembolism Pericarditis Cardiac tamponade / perforation Vascular access complications requiring intervention Heart block Late onset (any time during follow-up through 12 months) Pulmonary vein (PV) stenosis (> 70% diameter reduction from baseline) Atrio-esophageal fistula | 7-Days | 
| The proportion of subjects with a device- or procedure-related SAE | Proportion of subjects with one or more device or procedure related SAEs. | 12 Months | 
| The proportion of subjects with stroke or TIA | The proportion of subjects with stroke or TIA | 12 Months | 
| The proportion of subjects requiring cardioversions | The proportion of subjects requiring cardioversions | 12 Months | 
| The proportion of subjects requiring an arrhythmia-related (AF, AFL or AT) hospitalization | The proportion of subjects requiring an arrhythmia-related (AF, AFL or AT) hospitalization | 12 Months |