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

NCT ID: NCT06096337

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

484 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-28

Study Completion Date

2028-02-03

Brief Summary

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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.

Detailed Description

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

Once randomization is complete, additional subjects will be enrolled and sequentially assigned to receive PFA treatment to fulfill the number of subjects required for the Primary Safety Endpoint assessment. These additional subjects are referred to as PFA Assigned (Non-Roll-In) Subjects.

Subjects randomized or assigned 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). 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. 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".

Conditions

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Persistent Atrial Fibrillation

Keywords

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Persistent Atrial Fibrillation Insertable Cardiac Monitor Pulsed Field Ablation Atrial Fibrillation Cardiovascular Diseases Heart Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pulsed Field Ablation (PFA)

Pulsed Field Ablation (PFA) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)

Group Type EXPERIMENTAL

FARAPULSE™ Pulsed Field Ablation (PFA) System

Intervention Type DEVICE

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.

Anti-Arrhythmic Drug (AAD)

Anti-Arrhythmic Drug (AAD) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)

Group Type ACTIVE_COMPARATOR

Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, Dofetilide, and Dronedarone

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DEVICE

Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, Dofetilide, and Dronedarone

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years of age, or older if specified by local law
2. Have symptomatic persistent AF, confirmed by both:

a. 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 b. 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(i.e., within 180 days of consent

Exclusion Criteria

1. Treated with AAD (Class I or III) ≤ 6 months (i.e., within 180 days) before enrollment,

1. More than 7-day history of therapeutic AAD use (Class I or III), or
2. ≥ 24 hours amiodarone, i Note Pill-in-the-pocket AAD use, is permitted.
2. Treated with AAD ( Class I or III) \> 6 months (i.e., more than 180 days) before enrollment and experienced AAD failure (adverse drug effects or frequent AF episodes)
3. Contraindication to, or unwillingness to use, AADs (Class I and III, excluding amiodarone)
4. Contraindication to PFA treatment
5. Contraindication to, or unwillingness to use, systemic anticoagulation, or acceptable alternatives, pre-, intra-, and post-procedure to achieve adequate anticoagulation.
6. 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
7. 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
8. 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
9. Any of the following events 90 days prior to randomization (or Index procedure for PFA Assigned or 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
10. Known coagulopathy disorder (e.g., von Willbrand's disease, hemophilia)
11. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx™ ICM device
12. 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
13. Body Mass Index (BMI) \> 45
14. Solid organ or hematologic transplant, or currently being evaluated for a transplant
15. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis
16. Severe lung disease, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
17. Severe pulmonary hypertension during screening assessment
18. 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
19. Active malignancy at enrollment (other than cutaneous basal cell or squamous cell carcinoma)
20. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
21. Known active systemic infection
22. Uncontrolled diabetes mellitus or a recorded HgbA1c \> 8.0% in the 90 days prior to randomization (or Index procedure for PFA Assigned or roll-in subjects)
23. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (\>30 pauses per hour)
24. Predicted life expectancy less than one (1) year
25. 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
26. 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
27. Has operational LUX-Dx ICM that was inserted more than 6 months (i.e., \>180 days) prior to enrollment
28. Has operational ICM other than a LUX-Dx ICM and does not express a willingness to receive a LUX-Dx ICM for the study
29. 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.
30. AAD (Class I and III) Drug Naïve Subjects (as defined in criterion #1 and #2), who are PFA Assigned (Non-Roll-in), PFA randomized, or Roll-in with a CHA2DS2-VASc Score ≥ 4
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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Oussama Wazni, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner University Medical Center Phoenix

Phoenix, Arizona, United States

Site Status

Phoenix Cardiovascular Research Group

Phoenix, Arizona, United States

Site Status

Arrhythmia Research Group

Jonesboro, Arkansas, United States

Site Status

Scripps Memorial Hosptial

La Jolla, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Cardiology Associates Medical Group, Inc

Ventura, California, United States

Site Status

HCA Florida Mercy Hospital

Miami, Florida, United States

Site Status

Sarasota Memorial Hospital

Sarasota, Florida, United States

Site Status

Tallahassee Memorial Hospital

Tallahassee, Florida, United States

Site Status

St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

St. John's Hospital

Springfield, Illinois, United States

Site Status

Community Heart and Vascular Hospital

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

West Burlington, Iowa, United States

Site Status

Mercy Hospital Medical Center-Hospital

West Des Moines, Iowa, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Southcoast Physicians Group

Fall River, Massachusetts, United States

Site Status

University of Michigan Hospitals

Ann Arbor, Michigan, United States

Site Status

Corewell Health

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic Foundation-Hospital

Rochester, Minnesota, United States

Site Status

Catholic Medical Center

Manchester, New Hampshire, United States

Site Status

Valley Hospital

Paramus, New Jersey, United States

Site Status

Northwell Health

Bay Shore, New York, United States

Site Status

Kaleida Health

Buffalo, New York, United States

Site Status

Weill Cornell Medical University

New York, New York, United States

Site Status

Good Samaritan - Suffern

Suffern, New York, United States

Site Status

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

Bethesda North Hospital

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

OhioHealth Research and Innovation Institute - Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status

York Hospital

York, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Cardiac Arrhythmia Research

Austin, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Orion Medical

Houston, Texas, United States

Site Status

Christus Trinity Mother Frances Health System

Tyler, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Chippenham & Johnston-Willis Hospital (CJW)

Richmond, Virginia, United States

Site Status

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Royal Adelaide Hospital-Hospital

Adelaide, South Australia, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Medizinische Univ.-Kliniken Graz-Hospital

Graz, , Austria

Site Status

St. Jan

Bruges, , Belgium

Site Status

Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status

Institut universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, Canada

Site Status

Klinicki Bolnicki Centar Split

Split, , Croatia

Site Status

CHU Grenoble - Hopital Michallon

Grenoble, , France

Site Status

Cardioangiologisches Centrum Bethanien

Frankfurt, , Germany

Site Status

Staedtisches Klinikum Karlsruhe

Karlsruhe, , Germany

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Prince of Wales Hospital

Shatin, , Hong Kong

Site Status

AOU delle Marche - PO GM Lancisi

Ancona, AN, Italy

Site Status

Centro Cardiologico Monzino

Milan, MI, Italy

Site Status

Maria Cecilia Hospital SPA

Cotignola, RA, Italy

Site Status

Fondazione PTV - Policlinico Tor Vergata

Roma, , Italy

Site Status

National Heart Centre Singapore

Singapore, , Singapore

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Taipei Veterans General Hospital-Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Australia Austria Belgium Canada Croatia France Germany Hong Kong Italy Singapore Spain Taiwan

Other Identifiers

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PF303

Identifier Type: -

Identifier Source: org_study_id