Pulsed Field Ablation and Pulsed Field CRyoAbLation in PErsistent AtriaL FibrilLation

Study Overview
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Brief Summary
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A prospective, two-arm, multi-center, randomized, open-label, pre-market, First-in-Human clinical study designed to provide safety and performance data regarding the use of the Adagio PFA and PFCA Systems in the treatment of PsAF.

Detailed Description
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Enrolled subjects will be treated (ablation) with the Adagio PFA or PFCA System in a 1:1 randomized fashion. Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI), and CTI at the discretion and clinical judgment of the investigator. Data will be collected throughout 12-month follow up period to assess safety and performance of the device. Recurrence of atrial arrhythmias is measured by 12-lead ECGs and 48-hour continuous ECG recording (Holter).

Official Title
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PARALELL - Pulsed Field Ablation and Pulsed Field CRyoAbLation in PErsistent AtriaL FibrilLation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IC 1 Male or female between the ages of 18 - 80 years IC 2 Currently scheduled for an ablation of symptomatic persistent (> 7 days) atrial fibrillation within the past year documented by ECG or Continuous Holter monitoring IC 3 Refractory to at least one class I or III AAD. (Refractory defined as not effective or not tolerated) IC 4 Willingness, ability, and commitment to participate in baseline and follow-up evaluations for the full length of the study IC 5 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 Continuous AF lasting longer than 12-months EC 3 History of previous left atrial ablation or surgical treatment for AF/AFL/AT EC 4 AF 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 six (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 congenital anomaly EC 6 BMI > 40 EC 7 Any previous history of cryoglobulinemia (for those patients randomized to the PFCA arm) 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 Stroke or TIA within the last year. 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 conditions such as, mental illness, addictive disease, terminal illness with a life expectancy of less than two years, extensive travel away from the research center that may lead to non-compliance with the protocol procedure or follow up

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulsed Field Ablation (PFA) group<br>PsAF patients treated by PFA | Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.<br>* Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI). A right atrial cavo-tricuspid line for bi-directional block may be performed at discretion and clinical judgment of the investigator<br>|
| Experimental: Pulsed Field CryoAblation (PFCA) group<br>PsAF patients treated by PFCA | Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.<br>* Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI). A right atrial cavo-tricuspid line for bi-directional block may be performed at discretion and clinical judgment of the investigator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint for Safety | Analysis of the proportion of subjects who are free from device/procedure-related Major Adverse Events that occur during or following the ablation procedure | Up to 7 days following the ablation procedure | 
| Primary Procedural Performance Outcome | Analysis of the evidence of procedural electrical isolation of all pulmonary veins, posterior wall, and bidirectional block (if applicable) across all other ablation lines using the study device. | Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-Year Safety | Recording and analysis of all identified serious adverse events and serious adverse device effects through 12 months post-procedure. | 12 months | 
| One-Year Performance | Proportion of subjects receiving a single ablation procedure who has freedom from any documented left atrial arrhythmia (AF/AFL/AT) lasting longer than 30 seconds following the Blanking Period (3-months ± 14-days post index ablation) using a continuous 48-hour ECG recording through 12 months post-procedure. | 12 months | 
| Procedural Performance - ablation time | Ablation time defined as the total time for energy delivery to achieve PVI, PWI, and CTI (if applicable) | procedure | 
| Procedural Performance - procedure time | Total procedure time defined as the time from first venous access to the removal of the catheters from the heart at the end of the procedure | procedure | 
| Procedural Performance - fluoroscopy time | Procedure fluoroscopy time | procedure | 
| Procedural Performance - intraprocedural PV reconnection rate | The rate of intraprocedural PV reconnection - defined as confirmed conduction across a PVI line during the 20-minute waiting period to confirm PVI | procedure | 
| Procedural Performance - AAD use | Recording of the use of AADs in the follow up period beyond a 90-day blanking period | procedure and up to 12-month | 
| Procedural Performance - repeat ablation | Number of repeat ablations within and following the blanking period | procedure and up to 12-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulsed Field Ablation, Pulsed Field CryoAblation, Persistent AF, PFA, PFCA, AF, Adagio Medical