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

• ClinicalTrials.gov Identifier: NCT05443594
• Recruitment Status: Active, not recruiting
• First Posted: July 5, 2022
• Last Update Posted: April 8, 2024
• Sponsor: Boston Scientific Corporation
• Information provided by (Responsible Party): Boston Scientific Corporation

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Persistent Atrial Fibrillation	Device: Phase 1: FARAPULSE Ablation System; Device: Phase 2: FARAPULSE Ablation System	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 669 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation
• Actual Study Start Date: February 28, 2023
• Estimated Primary Completion Date: March 2025
• Estimated Study Completion Date: March 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Rate of Safety Events at 7 days Post Procedure [ Time Frame: 7 Days ]
   • 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
2. Phase 1: Rate of Safety Events at 30 days Post Procedure [ Time Frame: 30 Days ]
   • Cardiac tamponade / perforation
   • Pericarditis
3. Phase 1: Rate of Safety Events at 12 Months Post Procedure [ Time Frame: 360 Days ]
   • PV stenosis
   • Atrio-esophageal fistula
4. Phase 1: Rate of Persistent AF Acute Procedural Success [ Time Frame: 0 Days ]

   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
5. Phase 1: Rate of Persistent AF Chronic Success [ Time Frame: 360 Days ]

   Defined as the freedom from any of the following through the Day 360 Assessment after the Blanking Period, excluding documented CTI-dependent AFL:

   1. Arrhythmia: Occurrence of any Detectable AF, AFL or AT
   2. Re-ablation: Any re-ablation for AF, AFL or AT
   3. Cardioversion: Any electrical cardioversion for AF, AFL or AT
   4. AAD Use: Use of a Non-Failed Class I / III AAD or amiodarone
6. Phase 2: Rate of Safety Events at 7 days Post Procedure [ Time Frame: 7 Days ]
   • 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. Phase 2: Rate of Safety Events at 30 days Post Procedure [ Time Frame: 30 Days ]
   • Death
   • Cardiac tamponade / perforation
   • Pericarditis
   • Any PFA system related PFA procedure-related cardiovascular or pulmonary adverse event
8. Phase 2: Rate of Safety Events at 90 days Post Procedure [ Time Frame: 90 Days ]
   • PV stenosis
   • Atrio-esophageal fistula
9. Phase 2: Rate of Persistent AF Acute Procedural Success [ Time Frame: 0 Days ]
   • 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.
10. Phase 2: Rate of Persistent AF Chronic Success [ Time Frame: 360 Days ]

    Defined as the freedom from any of the following through the Day 360 Assessment after the Blanking Period, excluding documented CTI-dependent AFL:

    1. Arrhythmia: Occurrence of any Detectable AF, AFL or AT
    2. Re-ablation: Any re-ablation for AF, AFL or AT
    3. Cardioversion: Any electrical cardioversion for AF, AFL or AT
    4. AAD Use: Use of a Non-Failed Class I / III AAD or amiodarone

Eligibility Criteria

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

Criteria

[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

Contacts and Locations

Locations

United States, Alabama

Grandview Medical Center-Hospital

Birmingham, Alabama, United States, 35243

United States, Arizona

Banner University Medical Center Phoenix-Hospital

Phoenix, Arizona, United States, 85006

United States, Arkansas

Arrhythmia Research Group-Research Facility

Jonesboro, Arkansas, United States, 72401

United States, California

Scripps Memorial Hospital-Hospital

La Jolla, California, United States, 92037

Cedars - Sinai Medical Center-Hospital

Los Angeles, California, United States, 90048

University of California, San Francisco-Hospital

San Francisco, California, United States, 94143-0112

United States, Georgia

Emory University Hospital-Hospital

Atlanta, Georgia, United States, 30322

United States, Idaho

St. Lukes Idaho Cardiology Associates-Hospital

Boise, Idaho, United States, 83712

United States, Illinois

Northwestern University-Hospital

Evanston, Illinois, United States, 60208

St. John's Hospital-Hospital

Springfield, Illinois, United States, 62769

United States, Indiana

St. Vincent's Hospital-Hospital

Indianapolis, Indiana, United States, 46260

United States, Iowa

Mercy Hospital Medical Center-Hospital

West Des Moines, Iowa, United States, 50266

United States, Kansas

University of Kansas Hospital-Hospital

Kansas City, Kansas, United States, 66160

United States, Kentucky

Baptist Health Lexington

Lexington, Kentucky, United States, 40503

United States, Maryland

Johns Hopkins Hospital - East Baltimore Campus

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital-Hospital

Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital-Hospital

Boston, Massachusetts, United States, 02115

Lahey Clinic Hospital-Hospital

Burlington, Massachusetts, United States, 01805

United States, Missouri

St. Luke's Hospital of Kansas City-Hospital

Kansas City, Missouri, United States, 64111

United States, New Hampshire

Catholic Medical Center-Hospital

Manchester, New Hampshire, United States, 03102

United States, New Jersey

Valley Hospital-Hospital

Ridgewood, New Jersey, United States, 07450

United States, New York

NYU Langone Health Heart Rhythm Center

New York, New York, United States, 10016

Weill Cornell Medical University-Hospital

New York, New York, United States, 10021

Mount Sinai Medical Center-Hospital

New York, New York, United States, 10029

Lenox Hill Hospital

New York, New York, United States, 10075

St. Francis Hospital-Hospital

Roslyn, New York, United States, 11576

United States, Ohio

Bethesda North Hospital-Hospital

Cincinnati, Ohio, United States, 45242

Cleveland Clinic Foundation-Hospital

Cleveland, Ohio, United States, 44195

OhioHealth Research and Innovation Institute - Riverside Methodist Hospital-Hospital

Columbus, Ohio, United States, 43214

United States, Pennsylvania

Doylestown Hospital-Hospital

Doylestown, Pennsylvania, United States, 18901

UPMC Heart and Vascular Institute Harrisburg

Harrisburg, Pennsylvania, United States, 17101

Hospital of the University of Pennsylvania-Hospital

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Trident Medical Center-Hospital

Charleston, South Carolina, United States, 29406

United States, Tennessee

St. Thomas Research Institute, LLC-Hospital

Nashville, Tennessee, United States, 37205

Vanderbilt University Medical Center-Hospital

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Cardiac Arrhythmia Research-Hospital

Austin, Texas, United States, 78705

Orion Medical - Gulf Commerce Drive

Houston, Texas, United States, 77034

Christus Trinity Mother Frances Health System-Hospital

Tyler, Texas, United States, 75701

United States, Virginia

Sentara Norfolk General Hospital-Hospital

Norfolk, Virginia, United States, 23507

Virginia Commonwealth University Health System-Hospital

Richmond, Virginia, United States, 23219

Belgium

UZ Brussel (AZ VUB)-Hospital

Brussels, Belgium, 1090

Canada, Quebec

McGill University Health Centre-Hospital

Montreal, Quebec, Canada, H3G 1A4

Institut universitaire de Cardiologie et de Pneumologie de Quebec-Hospital

Ste-Foy, Quebec, Canada, G1V 4G5

Spain

Clinica Universidad de Navarra-Hospital

Pamplona, Spain, 31008

Sponsors and Collaborators

Boston Scientific Corporation

Investigators

• Principal Investigator: Vivek Reddy; MOUNT SINAI HOSPITAL

More Information

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT05443594
• Other Study ID Numbers: 92836802
• First Posted: July 5, 2022
• Last Update Posted: April 8, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes