Clinical trial NCT05443594: A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects with Persistent Atrial Fibrillation
Official title: A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects with Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Persistent Atrial Fibrillation
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2022-07-05
Enrollment: 669
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Phase 1: Rate of Safety Events at 7 days Post Procedure
timeFrame: 7 Days
measure: Phase 1: Rate of Safety Events at 30 days Post Procedure
timeFrame: 30 Days
measure: Phase 1: Rate of Safety Events at 12 Months Post Procedure
timeFrame: 360 Days
measure: Phase 1: Rate of Persistent AF Acute Procedural Success
timeFrame: 0 Days
measure: Phase 1: Rate of Persistent AF Chronic Success
timeFrame: 360 Days
measure: Phase 2: Rate of Safety Events at 7 days Post Procedure
timeFrame: 7 Days
measure: Phase 2: Rate of Safety Events at 30 days Post Procedure
timeFrame: 30 Days
measure: Phase 2: Rate of Safety Events at 90 days Post Procedure
timeFrame: 90 Days
measure: Phase 2: Rate of Persistent AF Acute Procedural Success
timeFrame: 0 Days
measure: Phase 2: Rate of Persistent AF Chronic Success
timeFrame: 360 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Center-Hospital
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix-Hospital
state: Arizona
city: Jonesboro
country: United States
facility: Arrhythmia Research Group-Research Facility
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Memorial Hospital-Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars - Sinai Medical Center-Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco-Hospital
state: California
city: Atlanta
country: United States
facility: Emory University Hospital-Hospital
state: Georgia
city: Boise
country: United States
facility: St. Lukes Idaho Cardiology Associates-Hospital
state: Idaho
city: Evanston
country: United States
facility: Northwestern University-Hospital
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital-Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent's Hospital-Hospital
state: Indiana
city: West Des Moines
country: United States
facility: Mercy Hospital Medical Center-Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Hospital-Hospital
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital - East Baltimore Campus
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital-Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital-Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic Hospital-Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City-Hospital
state: Missouri
city: Manchester
country: United States
facility: Catholic Medical Center-Hospital
state: New Hampshire
city: Ridgewood
country: United States
facility: Valley Hospital-Hospital
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health Heart Rhythm Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical University-Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center-Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital-Hospital
state: New York
city: Cincinnati
country: United States
facility: Bethesda North Hospital-Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation-Hospital
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research and Innovation Institute - Riverside Methodist Hospital-Hospital
state: Ohio
city: Doylestown
country: United States
facility: Doylestown Hospital-Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Heart and Vascular Institute Harrisburg
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania-Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Trident Medical Center-Hospital
state: South Carolina
city: Nashville
country: United States
facility: St. Thomas Research Institute, LLC-Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center-Hospital
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research-Hospital
state: Texas
city: Houston
country: United States
facility: Orion Medical - Gulf Commerce Drive
state: Texas
city: Tyler
country: United States
facility: Christus Trinity Mother Frances Health System-Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital-Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System-Hospital
state: Virginia
city: Brussels
country: Belgium
facility: UZ Brussel (AZ VUB)-Hospital
city: Montreal
country: Canada
facility: McGill University Health Centre-Hospital
state: Quebec
city: Ste-Foy
country: Canada
facility: Institut universitaire de Cardiologie et de Pneumologie de Quebec-Hospital
state: Quebec
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra-Hospital
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Vivek Reddy
role: PRINCIPAL_INVESTIGATOR
References: