Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF

Study Overview
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Brief Summary
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The study is a prospective, multi-center, non-randomized, unblinded worldwide pre-market clinical study. The purpose of the study is to provide data demonstrating the safety and effectiveness of the PulseSelect™ PFA System for the treatment of atrial fibrillation (AF). The study will also provide first in human insights into clinical safety and device function of the PulseSelect PFA System for pulmonary vein isolation (PVI) as a treatment for AF. To this end, the clinical study has been designed into phases (Pilot and Pivotal), with each phase comprising a separate data set that will be analyzed and reported on per the below objectives.

Official Title
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Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Failure of at least one AAD (class I or III) for AF as evidenced by recurrent symptomatic AF, or intolerable side effects due to AAD. A diagnosis of recurrent symptomatic paroxysmal or persistent AF: Symptomatic paroxysmal AF, which is defined as AF that terminates spontaneously or with intervention within 7 days of onset, documented by the following: physician's note indicating at least 2 symptomatic paroxysmal AF episodes occurring within 6 months prior to enrollment; and at least 1 ECG documented AF episode from any form of rhythm monitoring within 12 months prior to enrollment OR Symptomatic persistent AF, which is defined as continuous AF sustained beyond 7 days and less than 1 year, documented by the following: physician's note indicating at least 1 symptomatic persistent AF episode occurring within 6 months prior to enrollment; and any 24-hour continuous ECG recording documenting continuous AF within 6 months prior to enrollment; OR 2 ECGs from any form of rhythm monitoring taken at least 7 days apart, both showing continuous AF within 6 months prior to enrollment Age 18 through 80 years old (or older than 18 if required by local law) Exclusion Criteria: Long-standing persistent AF (continuous AF that is sustained >12 months) Left atrial diameter > 5.0 cm (anteroposterior) Prior left atrial ablation or surgical procedure (including left atrial appendage closures) Planned LAA closure procedure or implant of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) for any time during the follow-up period Patient who is not on oral anticoagulation therapy for at least 3 weeks prior to the ablation procedure Presence of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) Presence of any pulmonary vein stents Presence of any pre-existing pulmonary vein stenosis Pre-existing hemidiaphragmatic paralysis Presence of any cardiac valve prosthesis Moderate to severe mitral valve stenosis More than moderate mitral regurgitation (i.e., 3+ or 4+ MR) Any cardiac surgery, myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3-month interval preceding the consent date Unstable angina NYHA Class III or IV congestive heart failure or documented left ventricular ejection fraction (LVEF) less than or equal to 35% measure by acceptable cardiac testing (e.g. TTE) Primary pulmonary hypertension Rheumatic heart disease Thrombocytosis, thrombocytopenia Any condition contraindicating chronic anticoagulation Active systemic infection Hypertrophic cardiomyopathy Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, severe untreated obstructive sleep apnea, and acute alcohol toxicity Any cerebral ischemic event (strokes or TIAs) which occurred during the 6-month interval preceding the consent date History of thromboembolic event within the past 6 months or evidence of intracardiac thrombus at the time of the procedure Any woman known to be pregnant or breastfeeding, or any woman of childbearing potential who is not on a reliable form of birth regulation method or abstinence Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic Known allergies or hypersensitivities to adhesives Unwilling or unable to comply fully with study procedures and follow-up Unable to provide own informed consent

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study begins with a Pilot Phase, followed sequentially by a Pivotal Phase consisting of 3 arms enrolling simultaneously: Roll-in, Paroxysmal AF, Persistent AF
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pilot<br>First group of patients enrolled in the study. | Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System<br>* Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.<br>|
| Experimental: Pivotal - Roll-In<br>First patient treated by each physician in the pivotal phase. | Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System<br>* Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.<br>|
| Experimental: Pivotal - Paroxysmal AF<br>Non roll-in patients with paroxysmal AF (intermittent AF). | Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System<br>* Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.<br>|
| Experimental: Pivotal - Persistent AF<br>Non roll-in patients with persistent AF (AF that lasts longer than 7 days). | Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System<br>* Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: at Least One Primary Safety Event | Primary safety events are: Within 6 months post-ablation: Pulmonary vein stenosis (≥70% diameter reduction) Phrenic nerve injury/diaphragmatic paralysis (ongoing at 6 months) Atrioesophageal fistula Within 30 days of ablation procedure: Cardiac tamponade/perforation Cerebrovascular accident Major bleeding requiring transfusion Myocardial infarction Pericarditis requiring intervention Transient ischemic attack Vagal nerve injury resulting in esophageal dysmotility or gastroparesis Vascular access complications requiring intervention Systemic/pulmonary embolism requiring intervention Pulmonary edema Death Any PulseSelect PFA System-related or PFA procedure-related cardiovascular and/or pulmonary adverse event that prolongs or requires hospitalization for more than 48 hours (excluding recurrent AF/AFL/AT) | up to 6 months | 
| Effectiveness: Treatment Success. | Treatment success is defined as freedom from treatment failure. The study requires 24-hour Holter monitoring at 6 and 12 months in addition to weekly and symptomatic patient activated ambulatory monitoring transmissions through 12 months, and 12-lead ECGs at all follow up visits. Treatment failure is defined as any of the following components: Acute procedural failure Documented AF/AT/AFL on Holter/patient activated ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period. Any subsequent AF surgery or ablation in the left atrium, except for one repeat PVI ablation using PFA within the 90-day blanking period. Direct current cardioversion for atrial tachyarrhythmia recurrences after the 90-day blanking period. Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90-day blanking period. | up to 12 months |