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

NCT ID: NCT05443594

Last Updated: 2025-12-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

669 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-28

Study Completion Date

2025-02-11

Brief Summary

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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).

Detailed Description

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Conditions

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Persistent Atrial Fibrillation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pulsed Field Ablation (Phase 1)

PHASE 1 only

Group Type EXPERIMENTAL

Phase 1: FARAPULSE Ablation System

Intervention Type DEVICE

PHASE 1: Pulsed Field Ablation to isolate the Pulmonary Veins and Posterior Wall using the FARAPULSE Ablation System.

Pulsed Field Ablation (Phase 2)

PHASE 2 only

Group Type EXPERIMENTAL

Phase 2: FARAPULSE Ablation System

Intervention Type DEVICE

PHASE 2: Pulsed Field Ablation to isolate the Pulmonary Veins, Posterior Wall and Cavo-Tricuspid Isthmus using the FARAPULSE Ablation System.

Interventions

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Phase 1: FARAPULSE Ablation System

PHASE 1: Pulsed Field Ablation to isolate the Pulmonary Veins and Posterior Wall using the FARAPULSE Ablation System.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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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


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

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


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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston Scientific Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vivek Reddy

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

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Grandview Medical Center-Hospital

Birmingham, Alabama, United States

Site Status

Banner University Medical Center Phoenix-Hospital

Phoenix, Arizona, United States

Site Status

Arrhythmia Research Group-Research Facility

Jonesboro, Arkansas, United States

Site Status

Scripps Memorial Hospital-Hospital

La Jolla, California, United States

Site Status

Cedars - Sinai Medical Center-Hospital

Los Angeles, California, United States

Site Status

University of California, San Francisco-Hospital

San Francisco, California, United States

Site Status

Emory University Hospital-Hospital

Atlanta, Georgia, United States

Site Status

St. Lukes Idaho Cardiology Associates-Hospital

Boise, Idaho, United States

Site Status

Northwestern University-Hospital

Evanston, Illinois, United States

Site Status

St. John's Hospital-Hospital

Springfield, Illinois, United States

Site Status

St. Vincent's Hospital-Hospital

Indianapolis, Indiana, United States

Site Status

Mercy Hospital Medical Center-Hospital

West Des Moines, Iowa, United States

Site Status

University of Kansas Hospital-Hospital

Kansas City, Kansas, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

Johns Hopkins Hospital - East Baltimore Campus

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital-Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital-Hospital

Boston, Massachusetts, United States

Site Status

Lahey Clinic Hospital-Hospital

Burlington, Massachusetts, United States

Site Status

St. Luke's Hospital of Kansas City-Hospital

Kansas City, Missouri, United States

Site Status

Catholic Medical Center-Hospital

Manchester, New Hampshire, United States

Site Status

Valley Hospital-Hospital

Ridgewood, New Jersey, United States

Site Status

NYU Langone Health Heart Rhythm Center

New York, New York, United States

Site Status

Weill Cornell Medical University-Hospital

New York, New York, United States

Site Status

Mount Sinai Medical Center-Hospital

New York, New York, United States

Site Status

Lenox Hill Hospital

New York, New York, United States

Site Status

St. Francis Hospital-Hospital

Roslyn, New York, United States

Site Status

Bethesda North Hospital-Hospital

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation-Hospital

Cleveland, Ohio, United States

Site Status

OhioHealth Research and Innovation Institute - Riverside Methodist Hospital-Hospital

Columbus, Ohio, United States

Site Status

Doylestown Hospital-Hospital

Doylestown, Pennsylvania, United States

Site Status

UPMC Heart and Vascular Institute Harrisburg

Harrisburg, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania-Hospital

Philadelphia, Pennsylvania, United States

Site Status

Trident Medical Center-Hospital

Charleston, South Carolina, United States

Site Status

St. Thomas Research Institute, LLC-Hospital

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center-Hospital

Nashville, Tennessee, United States

Site Status

Texas Cardiac Arrhythmia Research-Hospital

Austin, Texas, United States

Site Status

Orion Medical - Gulf Commerce Drive

Houston, Texas, United States

Site Status

Christus Trinity Mother Frances Health System-Hospital

Tyler, Texas, United States

Site Status

Sentara Norfolk General Hospital-Hospital

Norfolk, Virginia, United States

Site Status

Virginia Commonwealth University Health System-Hospital

Richmond, Virginia, United States

Site Status

UZ Brussel (AZ VUB)-Hospital

Brussels, , Belgium

Site Status

McGill University Health Centre-Hospital

Montreal, Quebec, Canada

Site Status

Institut universitaire de Cardiologie et de Pneumologie de Quebec-Hospital

Ste-Foy, Quebec, Canada

Site Status

Clinica Universidad de Navarra-Hospital

Pamplona, , Spain

Site Status

Countries

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United States Belgium Canada Spain

References

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Matsumoto K, van Bragt KA, Kueffer FJ, Mburu W, Tarakji KG. Indirect treatment comparison of two pulsed field ablation systems for the treatment of persistent atrial fibrillation. J Interv Card Electrophysiol. 2025 Sep 10. doi: 10.1007/s10840-025-02124-6. Online ahead of print.

Reference Type DERIVED
PMID: 40928625 (View on PubMed)

Reddy VY, Gerstenfeld EP, Schmidt B, Nair D, Natale A, Saliba W, Verma A, Sommer P, Metzner A, Turagam M, Weiner S, Champagne J, Garcio-Bolao I, Calkins H, Olson J, Issa Z, Winner M, Su W, Tomassoni G, Kim J, Hook B, Delurgio DB, Gibson DN, Daccarett M, Patel C, Bhalla K, Shehata M, Harding JD, Cheung JW, Raybuck JD, Roelke S, Schwartz T, Sutton BS, Mansour M; ADVANTAGE-AF Investigators. Pulsed Field Ablation for Persistent Atrial Fibrillation: 1-Year Results of ADVANTAGE AF. J Am Coll Cardiol. 2025 May 6;85(17):1664-1678. doi: 10.1016/j.jacc.2025.03.515.

Reference Type DERIVED
PMID: 40306839 (View on PubMed)

Reddy VY, Gerstenfeld EP, Schmidt B, Andrade JG, Nair D, Natale A, Saliba W, Sommer P, Metzner A, Verma A, Hounshell T, Amin A, Gentlesk P, Weiner S, Cuoco FA, Kim J, Turagam MK, Tomassoni G, Patel C, Issa Z, Shehata M, Anderson AM, Stoltz TJ, Raybuck JD, Schwartz T, Sutton BS, Mansour M; ADVANTAGE AF Investigators. Pulsed Field Ablation of Persistent Atrial Fibrillation With Continuous Electrocardiographic Monitoring Follow-Up: ADVANTAGE AF Phase 2. Circulation. 2025 Jul 8;152(1):27-40. doi: 10.1161/CIRCULATIONAHA.125.074485. Epub 2025 Apr 24.

Reference Type DERIVED
PMID: 40273320 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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92836802

Identifier Type: -

Identifier Source: org_study_id