A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation (ADVANTAGE AF)

The objective of the ADVANTAGE AF Study is to establish the safety and effectiveness of the FARAPULSE Pulsed Field Ablation System (FARAPULSE PFA System) for treatment of drug resistant, symptomatic persistent atrial fibrillation (PersAF).

Study Overview

• Status: Active, not recruiting
• Conditions: Persistent Atrial Fibrillation
• Intervention / Treatment: Device: Phase 1: FARAPULSE Ablation System; Device: Phase 2: FARAPULSE Ablation System

• Study Type: Interventional
• Enrollment (Actual): 669
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie Roelke; Phone Number: +1 651-582-5077; Email: stephanie.roelke@bsci.com
• Study Contact Backup: Name: Thomas Stoltz; Phone Number: +1 651-582-5077; Email: thomas.stoltz@bsci.com

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • UZ Brussel (AZ VUB)-Hospital
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Centre-Hospital
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • Institut universitaire de Cardiologie et de Pneumologie de Quebec-Hospital
• Spain
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra-Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Medical Center-Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center Phoenix-Hospital
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Arrhythmia Research Group-Research Facility
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital-Hospital
    • Los Angeles, California, United States, 90048
      • Cedars - Sinai Medical Center-Hospital
    • San Francisco, California, United States, 94143-0112
      • University of California, San Francisco-Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital-Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Lukes Idaho Cardiology Associates-Hospital
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University-Hospital
    • Springfield, Illinois, United States, 62769
      • St. John's Hospital-Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent's Hospital-Hospital
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Mercy Hospital Medical Center-Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital-Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital - East Baltimore Campus
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital-Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital-Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Hospital-Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City-Hospital
  • New Hampshire
    • Manchester, New Hampshire, United States, 03102
      • Catholic Medical Center-Hospital
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital-Hospital
  • New York
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • New York, New York, United States, 10016
      • NYU Langone Health Heart Rhythm Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical University-Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center-Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital-Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital-Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation-Hospital
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research and Innovation Institute - Riverside Methodist Hospital-Hospital
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital-Hospital
    • Harrisburg, Pennsylvania, United States, 17101
      • UPMC Heart and Vascular Institute Harrisburg
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania-Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Trident Medical Center-Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Research Institute, LLC-Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center-Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research-Hospital
    • Houston, Texas, United States, 77034
      • Orion Medical - Gulf Commerce Drive
    • Tyler, Texas, United States, 75701
      • Christus Trinity Mother Frances Health System-Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital-Hospital
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Health System-Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

[PHASE 1] --------------------------------------------

Inclusion Criteria:

1. Age ≥ 18 years of age, or older if specified by local law

2. Subjects have symptomatic, documented, drug-resistant, Persistent AF, defined as:

   a. Documented: at a minimum a physician's note confirming the arrhythmia symptoms and durations AND, within 180 days of Enrollment Date, either: i. A 24-hour continuous ECG recording confirming continuous AF OR ii. Two ECGs from any regulatory cleared rhythm monitoring device showing continuous AF taken at least 7 days apart b. Drug-resistant: effectiveness failure of, intolerance to, or specific contraindication to at least one (1) AAD (Class I or III).

   c. Persistent: continuous AF for > 7 days and ≤ 365 days

3. Subjects who are willing and capable of providing informed consent
4. Subjects who are willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center

Exclusion Criteria:

1. Any of the following atrial conditions:

   1. Left atrial anteroposterior diameter ≥ 5.5 cm, or if LA diameter not available, non-indexed volume >100 ml (by MRI, CT or TTE report or physician note)
   2. Any prior atrial endocardial, epicardial or surgical ablation procedure for arrhythmia, other than right sided cavotricuspid isthmus ablation or for right sided SVT
   3. Current atrial myxoma
   4. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)
   5. Current left atrial thrombus

2. Cardiovascular exclusions - Any of the following CV conditions:

   a. History of sustained ventricular tachycardia or any ventricular fibrillation b. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes c. Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices, interatrial baffle, closure device, patch, or patent foramen ovale occluder, LA appendage closure, device or occlusion, active implantable loop recorder or insertable cardiac monitor at the time of ablation d. Valvular disease that is any of the following: i. Symptomatic ii. Causing or exacerbating congestive heart failure iii. Associated with abnormal LV function or hemodynamic measurements e. Hypertrophic cardiomyopathy f. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty g. Any IVC filter, known inability to obtain vascular access or other contraindication to femoral access h. Rheumatic heart disease i. Congenital heart disease with any clinically significant residual anatomic or conduction abnormality j. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months

3. Any of the following conditions at baseline (Section7.5):

   1. Heart failure associated with NYHA Class III or IV
   2. LVEF < 40%
   3. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two (2) BP measurements at baseline assessment

4. Any of the following events within 90 days of the Consent Date:

   1. Myocardial infarction (MI), unstable angina or coronary intervention
   2. Any cardiac surgery
   3. Heart failure hospitalization
   4. Pericarditis or symptomatic pericardial effusion
   5. Gastrointestinal bleeding
   6. Stroke, TIA, or intracranial bleeding
   7. Any non-neurologic thromboembolic event
   8. Carotid stenting or endarterectomy
5. Thrombocytosis, thrombocytopenia, disorder of blood clotting or bleeding diathesis
6. Contraindication to, or unwillingness to use, systemic anticoagulation
7. Patients who have not been on anticoagulation therapy for at least 4 weeks prior to the ablation procedure
8. 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

9. Health conditions that in the investigator's medical opinion 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) > 42.0
   2. Solid organ or hematologic transplant, or currently being evaluated for a transplant
   3. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis.
   4. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
   5. Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant
   6. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)
   7. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
   8. Active systemic infection
   9. COVID-19 disease

   i. 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 j. Uncontrolled diabetes mellitus or a recorded HgbA1c > 8.0% in the 90 days prior to the Consent Date k. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour)

10. Predicted life expectancy less than one (1) year
11. Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the Sponsor to determine eligibility

[PHASE 2] --------------------------------------------

Inclusion Criteria:

1. Age ≥ 18 years of age, or older if specified by local law

2. Subjects have symptomatic, documented, drug-resistant, Persistent AF, defined as:

   a. Documented: at a minimum a physician's note confirming the arrhythmia symptoms and durations AND, within 180 days of Enrollment Date, either: i. A 24-hour continuous ECG recording confirming continuous AF OR ii. Two ECGs from any regulatory cleared rhythm monitoring device showing continuous AF taken at least 7 days apart b. Drug-resistant: effectiveness failure of, intolerance to, or specific contraindication to at least one (1) AAD (Class I or III).

   c. Persistent: continuous AF for > 7 days and ≤ 365 days

3. Subjects who are willing and capable of providing informed consent
4. Subjects who are willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center

Exclusion Criteria:

1. Any of the following atrial conditions:

   1. Left atrial anteroposterior diameter ≥ 5.5 cm, or if LA diameter not available, non-indexed volume >100 ml (by MRI, CT or TTE report or physician note)
   2. Any prior atrial endocardial, epicardial or surgical ablation procedure for arrhythmia, other than right sided cavotricuspid isthmus ablation or for right sided SVT
   3. Current atrial myxoma
   4. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)
   5. Current left atrial thrombus

2. Cardiovascular exclusions - Any of the following CV conditions:

   1. History of sustained ventricular tachycardia or any ventricular fibrillation
   2. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes
   3. Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices, interatrial baffle, closure device, patch, or patent foramen ovale occluder, LA appendage closure, device or occlusion, active implantable loop recorder or insertable cardiac monitor at the time of ablation
   4. Valvular disease that is any of the following:

   i. Symptomatic ii. Causing or exacerbating congestive heart failure iii. Associated with abnormal LV function or hemodynamic measurements e. Hypertrophic cardiomyopathy f. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty g. Any IVC filter, known inability to obtain vascular access or other contraindication to femoral access h. Rheumatic heart disease i. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months j. Nitroglycerin intolerance: Known adverse drug reaction to nitroglycerin k. Coronary disease: Known severe non-revascularizable coronary disease l. Stents: Pre-existing right coronary artery stent

3. Any of the following conditions at baseline (Section7.5):

   1. Heart failure associated with NYHA Class III or IV
   2. LVEF < 40%
   3. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two (2) BP measurements at baseline assessment
   4. Ventricular dysfunction: Right ventricular dysfunction

4. Any of the following events within 90 days of the Consent Date:

   1. Myocardial infarction (MI), unstable angina or coronary intervention
   2. Any cardiac surgery
   3. Heart failure hospitalization
   4. Pericarditis or symptomatic pericardial effusion
   5. Gastrointestinal bleeding
   6. Stroke, TIA, or intracranial bleeding
   7. Any non-neurologic thromboembolic event
   8. Carotid stenting or endarterectomy
5. Thrombocytosis, thrombocytopenia, disorder of blood clotting or bleeding diathesis
6. Contraindication to, or unwillingness to use, systemic anticoagulation
7. Patients who have not been on anticoagulation therapy for at least 4 weeks prior to the ablation procedure
8. 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

9. Health conditions that in the investigator's medical opinion 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) > 42.0
   2. Solid organ or hematologic transplant, or currently being evaluated for a transplant
   3. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis.
   4. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
   5. Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant
   6. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)
   7. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
   8. Active systemic infection
   9. COVID-19 disease

   i. 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 j. Uncontrolled diabetes mellitus or a recorded HgbA1c > 8.0% in the 90 days prior to the Consent Date k. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour) l. Medication Use: Required use of phosphodiesterase inhibitors within 24 hours of the ablation procedure

10. Predicted life expectancy less than one (1) year
11. Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the Sponsor to determine eligibility

12. Any of the following congenital conditions:

    1. Congenital heart disease: Congenital heart disease with any clinically significant residual anatomic or conduction abnormality
    2. Methemoglobinemia: History of known congenital methemoglobinemia
    3. G6PD deficiency: History of known G6PD deficiency
13. Contraindication to ICM insertion: Patients who cannot tolerate a subcutaneous, chronically-inserted LUX-Dx device
14. LUX-Dx longevity: Patients with a LUX-Dx device inserted > 6 months prior to enrollment with an estimated longevity of less than 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pulsed Field Ablation (Phase 1); PHASE 1 only	Device: Phase 1: FARAPULSE Ablation System; PHASE 1: Pulsed Field Ablation to isolate the Pulmonary Veins and Posterior Wall using the FARAPULSE Ablation System.
Experimental: Pulsed Field Ablation (Phase 2); PHASE 2 only	Device: Phase 2: FARAPULSE Ablation System; PHASE 2: Pulsed Field Ablation to isolate the Pulmonary Veins, Posterior Wall and Cavo-Tricuspid Isthmus using the FARAPULSE Ablation System.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Rate of Safety Events at 7 days Post Procedure	Death; Myocardial infarction; Stroke; TIA; Peripheral or organ thromboembolism; Pulmonary edema; Unresolved phrenic nerve palsy / paresis; Vascular access complications; Heart block; Gastric motility / pyloric spasm disorders	7 Days
Phase 1: Rate of Safety Events at 30 days Post Procedure	Cardiac tamponade / perforation; Pericarditis	30 Days
Phase 1: Rate of Safety Events at 12 Months Post Procedure	PV stenosis; Atrio-esophageal fistula	360 Days
Phase 1: Rate of Persistent AF Acute Procedural Success	Using only the FARAWAVE Catheter, Acute Procedural Success is defined as: The isolation of all attempted Pulmonary Veins as clinically assessed at the end of the procedure by entrance block, AND; The isolation of the Left Atrial Posterior Wall as clinically assessed at the end of the procedure via interrogation by multipolar diagnostic catheter or 3D electroanatomical mapping	0 Days
Phase 1: Rate of Persistent AF Chronic Success	Defined as the freedom from any of the following through the Day 360 Assessment after the Blanking Period, excluding documented CTI-dependent AFL: Arrhythmia: Occurrence of any Detectable AF, AFL or AT; Re-ablation: Any re-ablation for AF, AFL or AT; Cardioversion: Any electrical cardioversion for AF, AFL or AT; AAD Use: Use of a Non-Failed Class I / III AAD or amiodarone	360 Days
Phase 2: Rate of Safety Events at 7 days Post Procedure	Myocardial infarction; Stroke; Transient Ischemic Attack (TIA); Peripheral or organ thromboembolism; Pulmonary edema; Unresolved phrenic nerve palsy / paresis; Vascular access complications; Heart block; Gastric motility / pyloric spasm disorders	7 Days
Phase 2: Rate of Safety Events at 30 days Post Procedure	Death; Cardiac tamponade / perforation; Pericarditis; Any PFA system related PFA procedure-related cardiovascular or pulmonary adverse event	30 Days
Phase 2: Rate of Safety Events at 90 days Post Procedure	PV stenosis; Atrio-esophageal fistula	90 Days
Phase 2: Rate of Persistent AF Acute Procedural Success	The isolation of all attempted PVs as clinically assessed at the end of the procedure by entrance block performed with or without adenosine testing, AND; The isolation of the left atrial PW as clinically assessed at the end of the procedure, performed with or without adenosine testing, via interrogation by multipolar diagnostic catheter or 3D electroanatomical mapping.	0 Days
Phase 2: Rate of Persistent AF Chronic Success	Defined as the freedom from any of the following through the Day 360 Assessment after the Blanking Period, excluding documented CTI-dependent AFL: Arrhythmia: Occurrence of any Detectable AF, AFL or AT; Re-ablation: Any re-ablation for AF, AFL or AT; Cardioversion: Any electrical cardioversion for AF, AFL or AT; AAD Use: Use of a Non-Failed Class I / III AAD or amiodarone	360 Days

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Vivek Reddy, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 92836802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes