Pulsed Field Ablation (PFA) Versus Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation

Persistent Atrial Fibrillation Clinical Trial

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Official title:

A Prospective Randomized Multicenter Global Study Comparing Pulsed Field Ablation (PFA) Versus Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06096337
• Other study ID #: PF303
• Status: Recruiting
• Phase: N/A
• Start date: December 28, 2023
• Est. completion date: December 30, 2027

Study information

• Verified date: June 2024
• Source: Boston Scientific Corporation
• Contact: Boston Scientific
• Phone: 800-272-1001
• Email: monitortroubleshooting[@]cdxbsci.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to establish the safety and effectiveness of pulsed field ablation as a first-line ablation treatment for subjects with persistent atrial fibrillation as compared to subjects who received an initial treatment with anti-arrhythmic drugs.

Description:

This is a prospective, randomized, multi-center, global, pivotal Investigational device exemption (IDE) study. Subjects with persistent atrial fibrillation will be randomized to either pulsed field ablation (PFA) or Versus Anti-Arrhythmic Drug (AAD) treatment.

Subjects randomized to PFA treatment will undergo percutaneous ablative pulmonary vein isolation (PVI) and left atrial posterior wall isolation (PWI) using the FARAWAVE™ PFA Catheter (first-line ablation cohort).

Subjects randomized to AAD treatment will be prescribed and monitored in accordance with local clinical practice and already established guideline-directed therapy for patients with persistent atrial fibrillation (AF). Cardioversion is recommended during the initiation of antiarrhythmic drugs for subjects who are not in sinus rhythm. In the case of clinical inefficacy, the AAD dose will be up-titrated to the maximum tolerated dose. Thereafter, a change to a second or to a third AAD should be undertaken, insofar as the subject remains within the blanking period, with the goal to completely suppress AF episodes ≥ 30 seconds in duration. It is advisable to perform cardioversion with each dose titration or when changing the AAD regimen. If AAD treatment is proven to be ineffective or intolerable outside of the blanking period, subjects can undergo subsequent ablation therapy and be considered part of the "delayed ablation cohort".

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 387
• Est. completion date: December 30, 2027
• Est. primary completion date: December 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

• 2. Have symptomatic persistent AF, confirmed by both:

1. Documentation, within 180 days of randomization, or treatment assignment for roll-in subjects, of either: i. A 24-hour continuous ECG recording (from any regulatory cleared rhythm monitoring device) confirming continuous AF, OR ii. Two ECGs (from any regulatory cleared rhythm monitoring device) showing continuous AF taken at least 7 days apart

2. Documentation, such as physician note, of persistent continuous AF for > 7 days and = 365 days

• 3. Willing and capable of providing informed consent

• 4. Willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center

• 5. Willing to receive LUX-Dx™ insertable cardiac monitor (ICM) during the study or already has a LUX-Dx™ ICM that was inserted = 6 months of consent

Exclusion Criteria:

• 1. Over the 6 months preceding enrollment, more than 7-day history of therapeutic AAD use (Class I or III), or = 24 hours amiodarone, except for pill-in-the-pocket AAD use, which is permitted. Or, treated with AAD > 6 months preceding enrollment and experienced AAD failure (adverse drug effects or frequent AF episodes)

• 2. Any of the following atrial conditions:

1. Left atrial (LA) anteroposterior diameter = 5.5 cm, or, if LA diameter not available, non-indexed volume >100 ml, as documented by physician note or imaging (Note: if both values are available, only the LA diameter will be used to confirm eligibility criteria)

2. Any prior atrial endocardial, epicardial or surgical ablation procedure for arrhythmia, other than right sided cavotricuspid isthmus ablation or for right sided supraventricular tachycardia

3. Current atrial myxoma

4. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)

5. Current left atrial thrombus

• 3. Any of the following cardiovascular 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, atrial septal patch, atrial septal defect closure device, or patent foramen ovale occluder

4. Valvular disease that is any of the following: i. Symptomatic, ii. Causing or exacerbating congestive heart failure, iii. Associated with abnormal left ventricular (LV) function or hemodynamic measurements

5. Hypertrophic cardiomyopathy

6. Cardiac amyloidosis

7. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty

8. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication to femoral access

9. Rheumatic heart disease

10. Congenital heart disease with any clinically significant residual anatomic or conduction abnormality

11. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months

• 4. Any of the following conditions identified during screening assessments

1. Heart failure associated with New York Heart Association (NYHA) Class IV

2. Left Ventricle Ejection Fraction (LVEF) < 40%

3. Uncontrolled hypertension (Systolic Blood Pressure > 160 mmHg or Diastolic Blood Pressure > 95 mmHg on two (2) BP measurements during screening

• 5. Any of the following events 90 days prior to randomization (or Index procedure for roll-in subjects):

1. Myocardial infarction (MI), unstable angina or coronary intervention

2. Cardiac surgery

3. Heart failure hospitalization

4. Pericarditis or symptomatic pericardial effusion

5. Gastrointestinal bleeding

6. Stroke, TIA, or intracranial bleeding

7. Non-neurologic thromboembolic event

8. Carotid stenting or endarterectomy

• 6. Thrombocytosis, thrombocytopenia, disorder of blood clotting or bleeding diathesis

• 7. Contraindication to, or unwillingness to use, systemic anticoagulation, AADs (Class I and III, excluding amiodarone which is not allowed during the study), and PFA treatment

• 8. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx™ ICM device

• 9. Women of childbearing potential who are pregnant, lactating, not using a reliable form of contraception, or who are planning to become pregnant during the anticipated study period

• 10. Body Mass Index (BMI) > 45

• 11. Solid organ or hematologic transplant, or currently being evaluated for a transplant

• 12. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis

• 13. Severe lung disease, or any lung disease involving abnormal blood gases or requiring supplemental oxygen

• 14. Severe pulmonary hypertension during screening assessment

• 15. 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

• 16. Active malignancy at enrollment (other than cutaneous basal cell or squamous cell carcinoma)

• 17. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration

• 18. Known active systemic infection

• 19. Known positive test for Coronavirus Disease 2019 (COVID-19) and disease not clinically resolved

• 20. Uncontrolled diabetes mellitus or a recorded HgbA1c > 8.0% in the 90 days prior to randomization (or Index procedure for roll-in subjects)

• 21. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour)

• 22. Predicted life expectancy less than one (1) year

• 23. Currently enrolled in another investigational study or registry that would directly interfere with this 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

• 24. 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

• 25. Has operational LUX-Dx ICM that was inserted more than 6 months prior to enrollment

• 26. Has operational ICM other than a LUX-Dx ICM and does not express a willingness to receive a LUX-Dx ICM for the study

• 27. Individuals who may require an ablation, besides the PV and PW, in the left atrium including, but not limited to, those with Left-Sided Atrioventricular Reentrant Tachycardia (AVRT), Left-Sided Atrial Tachycardia (AT), or Atypical Left-Sided Atrial Flutter.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Persistent Atrial Fibrillation

Intervention

Device:
• FARAPULSE™ Pulsed Field Ablation (PFA) System
Subjects will undergo a pulsed field ablation procedure using the FARAPULSE™ Pulsed Field Ablation (PFA) System for the isolation of pulmonary veins and posterior wall.

Drug:
• Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, and Dofetilide
Anti-Arrhythmic Drugs (AADs) including, Flecainide, Sotalol, Propafenone, and Dofetilide will be prescribed and monitored in accordance with local clinical practice and already established guideline-directed therapy for patients with persistent atrial fibrillation (AF).

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Belgium	St. Jan	Brugge
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Institut universitaire de Cardiologie et de Pneumologie de Quebec	Québec	Quebec
Canada	Vancouver General Hospital	Vancouver
Croatia	Klinicki Bolnicki Centar Split	Split
Germany	Cardioangiologisches Centrum Bethanien	Frankfurt
Italy	AOU delle Marche - PO GM Lancisi	Ancona	AN
Italy	Maria Cecilia Hospital SPA	Cotignola	RA
Italy	Centro Cardiologico Monzino	Milano	MI
Singapore	National Heart Centre Singapore	Singapore
Spain	Hospital Universitario La Fe	Valencia
United States	University of Michigan Hospitals	Ann Arbor	Michigan
United States	Memorial Mission Hospital-Hospital	Asheville	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	Texas Cardiac Arrhythmia Research	Austin	Texas
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Northwell Health	Bay Shore	New York
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Kaleida Health	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	OhioHealth Research and Innovation Institute - Riverside Methodist Hospital	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas Medical Branch	Galveston	Texas
United States	Corewell Health	Grand Rapids	Michigan
United States	Orion Medical	Houston	Texas
United States	Community Heart and Vascular Hospital	Indianapolis	Indiana
United States	Arrhythmia Research Group	Jonesboro	Arkansas
United States	Catholic Medical Center	Manchester	New Hampshire
United States	HCA Florida Mercy Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Weill Cornell Medical University	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
United States	Banner University Medical Center Phoenix	Phoenix	Arizona
United States	Phoenix Cardiovascular Research Group	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Southcoast Physicians Group	Providence	Rhode Island
United States	Chippenham & Johnston-Willis Hospital (CJW)	Richmond	Virginia
United States	Mayo Clinic Foundation-Hospital	Rochester	Minnesota
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	St. John's Hospital	Springfield	Illinois
United States	Good Samaritan - Suffern	Suffern	New York
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	St. Joseph's Hospital	Tampa	Florida
United States	Oklahoma Heart Institute	Tulsa	Oklahoma
United States	Christus Trinity Mother Frances Health System	Tyler	Texas
United States	Cardiology Associates Medical Group, Inc	Ventura	California
United States	University of Iowa Hospitals and Clinics	West Burlington	Iowa
United States	Mercy Hospital Medical Center-Hospital	West Des Moines	Iowa
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Croatia,  Germany,  Italy,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of intent to treat subjects, randomized to PFA with PFA System inserted into body, during index procedure or repeat PFA procedure during blanking period, with device or procedure-related Composite Adverse Events that is serious.	Composite Adverse Events are defined as follows: Day 0 through Day 7: Gastric motility / pyloric spasm disorders; Heart block; Myocardial infarction; Peripheral or organ thromboembolism; Pulmonary edema; Stroke/ Cerebrovascular accident (CVA); Transient ischemic attack (TIA); Unresolved phrenic nerve palsy / paresis; Vascular access complications; Day 0 through Day 30: Cardiac tamponade / perforation; Cardiovascular or pulmonary adverse event; Death; Pericarditis; Day 0 through Month 12; Atrio-esophageal fistula; Pulmonary vein stenosis	12-Months
Primary	Rate of intent to treat subjects with treatment success from the pulse field ablation treatment and Anti-Arrhythmic Drug treatment.	Rate of Intent to Treat subjects with Treatment Success through Month 12 assessment; PFA Treatment Arm: Acute Success - Isolation of all attempted pulmonary veins and left atrial posterior wall with PFA system; Chronic Success: Freedom from amiodarone use and after the blanking period through the Month-12 assessment occurrence of: Occurrence = 1 hour of asymptomatic or = 30 seconds of symptomatic Atrial Fibrillation (AF), Atrial Flutter (AFL), or Atrial Tachycardia (AT); Any re-ablation for AF, AFL, or AT; Any electrical cardioversion for AF, AFL, or AT; Any Class I or III AAD use; AAD Treatment Arm: Acute Success - Ablation not performed during the blanking period; Chronic Success - Freedom from amiodarone use and after the blanking period through the Month 12 assessment of occurrence of: Detectable occurrence = 1 hour of asymptomatic or = 30 seconds of symptomatic AF, AFL, or AT; Electrical cardioversion for AF, AFL, or AT; Any ablation for AF, AFL, or AT	12-Months
Secondary	Atrial fibrillation burden between the pulsed field ablation and anti-arrhythmic drug arm, as measured by the LUX-Dx Insertable Cardiac Monitor and defined as the proportion of time an individual spends in AF during a period (expressed as a percentage).	Atrial Fibrillation (AF) burden, as measured by the LUX-Dx Insertable Cardiac Monitor (ICM) between the 2 randomized groups: Pulsed Field Ablation (PFA) as initial treatment for subjects with persistent AF; Anti-Arrhythmic Drug (AAD) as initial treatment for subjects with persistent AF; AF Burden is defined as the proportion of time an individual spends in AF during a period (expressed as a percentage).	12, 24, and 36 Months