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

Persistent Atrial Fibrillation Clinical Trial

— ADVANTAGE AF  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05443594
• Other study ID #: 92836802
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 28, 2023
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 669
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

[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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Persistent Atrial Fibrillation

Intervention

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

Locations

Country	Name	City	State
Belgium	UZ Brussel (AZ VUB)-Hospital	Brussels
Canada	McGill University Health Centre-Hospital	Montreal	Quebec
Canada	Institut universitaire de Cardiologie et de Pneumologie de Quebec-Hospital	Ste-Foy	Quebec
Spain	Clinica Universidad de Navarra-Hospital	Pamplona
United States	Emory University Hospital-Hospital	Atlanta	Georgia
United States	Texas Cardiac Arrhythmia Research-Hospital	Austin	Texas
United States	Johns Hopkins Hospital - East Baltimore Campus	Baltimore	Maryland
United States	Grandview Medical Center-Hospital	Birmingham	Alabama
United States	St. Lukes Idaho Cardiology Associates-Hospital	Boise	Idaho
United States	Brigham and Women's Hospital-Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital-Hospital	Boston	Massachusetts
United States	Lahey Clinic Hospital-Hospital	Burlington	Massachusetts
United States	Trident Medical Center-Hospital	Charleston	South Carolina
United States	Bethesda North Hospital-Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Foundation-Hospital	Cleveland	Ohio
United States	OhioHealth Research and Innovation Institute - Riverside Methodist Hospital-Hospital	Columbus	Ohio
United States	Doylestown Hospital-Hospital	Doylestown	Pennsylvania
United States	Northwestern University-Hospital	Evanston	Illinois
United States	UPMC Heart and Vascular Institute Harrisburg	Harrisburg	Pennsylvania
United States	Orion Medical - Gulf Commerce Drive	Houston	Texas
United States	St. Vincent's Hospital-Hospital	Indianapolis	Indiana
United States	Arrhythmia Research Group-Research Facility	Jonesboro	Arkansas
United States	St. Luke's Hospital of Kansas City-Hospital	Kansas City	Missouri
United States	University of Kansas Hospital-Hospital	Kansas City	Kansas
United States	Scripps Memorial Hospital-Hospital	La Jolla	California
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Cedars - Sinai Medical Center-Hospital	Los Angeles	California
United States	Catholic Medical Center-Hospital	Manchester	New Hampshire
United States	St. Thomas Research Institute, LLC-Hospital	Nashville	Tennessee
United States	Vanderbilt University Medical Center-Hospital	Nashville	Tennessee
United States	Lenox Hill Hospital	New York	New York
United States	Mount Sinai Medical Center-Hospital	New York	New York
United States	NYU Langone Health Heart Rhythm Center	New York	New York
United States	Weill Cornell Medical University-Hospital	New York	New York
United States	Sentara Norfolk General Hospital-Hospital	Norfolk	Virginia
United States	Hospital of the University of Pennsylvania-Hospital	Philadelphia	Pennsylvania
United States	Banner University Medical Center Phoenix-Hospital	Phoenix	Arizona
United States	Virginia Commonwealth University Health System-Hospital	Richmond	Virginia
United States	Valley Hospital-Hospital	Ridgewood	New Jersey
United States	St. Francis Hospital-Hospital	Roslyn	New York
United States	University of California, San Francisco-Hospital	San Francisco	California
United States	St. John's Hospital-Hospital	Springfield	Illinois
United States	Christus Trinity Mother Frances Health System-Hospital	Tyler	Texas
United States	Mercy Hospital Medical Center-Hospital	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1: Rate of Safety Events at 30 days Post Procedure	Cardiac tamponade / perforation; Pericarditis	30 Days
Primary	Phase 1: Rate of Safety Events at 12 Months Post Procedure	PV stenosis; Atrio-esophageal fistula	360 Days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Phase 2: Rate of Safety Events at 90 days Post Procedure	PV stenosis; Atrio-esophageal fistula	90 Days
Primary	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
Primary	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