The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation

A Prospective Randomized Pivotal Trial of the FARAPULSE Pulsed Field Ablation System Compared With Standard of Care Ablation in Patients With Paroxysmal Atrial Fibrillation

This is a prospective, adaptive, multi-center, randomized safety and effectiveness pivotal study comparing the FARAPULSE Pulsed Field Ablation System with standard of care ablation with force-sensing RF catheters and cryoballoon catheters indicated for the treatment of PAF.

Key inclusion criteria: Patients are required to meet all the following inclusion criteria to participate in this study:

1. Patients with drug-resistant symptomatic PAF meeting all the following criteria:

   a. Paroxysmal: AF that terminates spontaneously or with intervention within 7 days of onset.

   b. Frequency: i. Physician documentation of recurrent PAF (two or more episodes) within 6 months, AND

   ii. At least one (1) documented episode by a recording such as ECG, EM, Holter monitor or telemetry strip within 12 months of enrollment.

   c. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least one (1) AAD (Class I to IV) for efficacy and / or intolerance.

2. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment.

3. Patient who are willing and capable of:

   1. Providing informed consent to undergo study procedures AND

   2. Participating in all examinations and follow-up visits and tests associated with this clinical study.

      Key exclusion criteria:

      Patients will be excluded from participating in this study if they meet any one of the following exclusion criteria:

      • 1. AF that is any of the following:
   1. Persistent (both early and longstanding) by diagnosis or continuous duration > 7 days
   2. Requires four (4) or more direct-current cardioversions in the preceding 12 months
   3. Secondary to electrolyte imbalance, thyroid disease, alcohol or other reversible / non-cardiac causes

2. Any of the following atrial conditions:

1. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT or TTE)

2. Any prior atrial endocardial or epicardial ablation procedure, other than right sided cavotricuspid isthmus ablation or for right sided SVT

3. Any prior atrial surgery

4. Intra-atrial septal patch or interatrial shunt

5. Atrial myxoma

6. Current LA thrombus

7. LA appendage closure, device or occlusion, past or anticipated

8. Any PV abnormality, stenosis or stenting (common and middle PVs are admissible)

   3. At any time, one (1) or more of the following cardiovascular procedures, implants or conditions:

a. Sustained ventricular tachycardia or any ventricular fibrillation

b. Hemodynamically significant valvular disease:

i. Valvular disease that is symptomatic

ii. Valvular disease causing or exacerbating congestive heart failure

iii. Aortic stenosis: if already characterized, valve area < 1.5cm or gradient > 20 mm Hg

iv. Mitral stenosis: if already characterized, valve area < 1.5cm or gradient > 5 mm Hg

v. Aortic or mitral regurgitation associated with abnormal LV function or hemodynamic measurements

c. Hypertrophic cardiomyopathy

d. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty

e. Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices

f. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication to femoral access

g. History of rheumatic fever

h. History of congenital heart disease with any residual anatomic or conduction abnormality

4. Any of the following procedures, implants or conditions:

1. At baseline:

i. New York Heart Association (NYHA) Class III/IV

ii. Left ventricular ejection fraction (LVEF) < 40%

iii. Symptomatic hypotension

iv. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two BP measurements at baseline assessment)

v. Symptomatic resting bradycardia

vi. Implantable loop recorder or insertable cardiac monitor,

b. Within the 3 months preceding the Consent Date:

i. Myocardial infarction

ii. Unstable angina

iii. Percutaneous coronary intervention

iv. Heart failure hospitalization

v. Treatment with amiodarone

vi. Pericarditis or symptomatic pericardial effusion

vii. Gastrointestinal bleeding

c. Within the 6 months preceding the Consent Date:

i. Heart surgery

ii. Stroke, TIA or intracranial bleeding

iii. Any thromboembolic event

iv. Carotid stenting or endarterectomy

5. Diagnosed disorder of blood clotting or bleeding diathesis

6. Contraindication to, or unwillingness to use, systemic anticoagulation

7. Patient who is not on anticoagulation therapy for at least 3 weeks prior to the ablation procedure

8. Contraindication to both CT and MRI

9. Sensitivity to contrast media not controllable by premedication

10. Women of childbearing potential who are pregnant, lactating, not using medical birth control or who are planning to become pregnant during the anticipated study period

11. Medical conditions that would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or modify outcome data or its interpretation, including but not limited to:

1. Body Mass Index (BMI) > 40.0
2. Solid organ or hematologic transplant, or currently being evaluated for an organ transplant
3. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
4. Renal insufficiency with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant
5. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)
6. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
7. Active systemic infection
8. COVID-19 disease
9. Current confirmed, active COVID-19 disease

ii. Current positive test for SARS-CoV-2

iii. Confirmed COVID-19 disease not clinically resolved at least 3 months prior to the Consent Date.

i. Other uncontrolled medical conditions that may modify device effect or increase risk, including uncontrolled diabetes mellitus (HgbA1c > 8.0% if test result already obtained) or active alcohol abuse

j. Sleep apnea and:

i. An apnea-hypopnea index (AHI) ≥ 15, or

ii. An AHI of ≥ 5 and ≤14 with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease or history of stroke, unless compliant with continuous positive airway pressure (CPAP) treatment.

k. Predicted life expectancy less than one (1) year

12. Clinically significant psychological condition that in the Investigator's opinion would prohibit the subject's ability to meet the protocol requirements

13. Current or anticipated enrollment in any other randomized, interventional or Food and Drug Administration (FDA)-regulated clinical study (data collection for registries or retrospective studies is permitted)

14. Employees / family members of:

1. FARAPULSE or any of its affiliates or contractors
2. The Investigator, sub-Investigators, or their medical office or practice, or healthcare organizations at which study procedures may be performed