Clinical trial NCT06096337: Pulsed Field Ablation (PFA) vs Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Persistent Atrial Fibrillation
Keywords: Persistent Atrial Fibrillation
Insertable Cardiac Monitor
Pulsed Field Ablation
Atrial Fibrillation
Cardiovascular Diseases
Heart Diseases
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 484
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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".

Eligibility criteria: 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

Primary outcomes:
measure: Rate of randomized PFA or PFA Assigned subjects with PFA System inserted into the body, during the index or repeat PFA procedure during blanking period, with device or procedure-related Composite Adverse Events that is serious.
timeFrame: 12-Months
measure: Rate of intent to treat subjects with treatment success from the pulse field ablation treatment and Anti-Arrhythmic Drug treatment.
timeFrame: 12-Months
Secondary outcomes:
measure: Atrial fibrillation burden between the pulsed field ablation and anti-arrhythmic drug arm, as the LUX-Dx Insertable Cardiac Monitor measures and defined as proportion of time individual spends in AF during a period (expressed as a percentage).
timeFrame: 12, 24, and 36 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Jonesboro
country: United States
facility: Arrhythmia Research Group
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Memorial Hosptial
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Ventura
country: United States
facility: Cardiology Associates Medical Group, Inc
state: California
city: Miami
country: United States
facility: HCA Florida Mercy Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Springfield
country: United States
facility: St. John's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Community Heart and Vascular Hospital
state: Indiana
city: West Burlington
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: West Des Moines
country: United States
facility: Mercy Hospital Medical Center-Hospital
state: Iowa
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Fall River
country: United States
facility: Southcoast Physicians Group
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Foundation-Hospital
state: Minnesota
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Paramus
country: United States
facility: Valley Hospital
state: New Jersey
city: Bay Shore
country: United States
facility: Northwell Health
state: New York
city: Buffalo
country: United States
facility: Kaleida Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medical University
state: New York
city: Suffern
country: United States
facility: Good Samaritan - Suffern
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research and Innovation Institute - Riverside Methodist Hospital
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Orion Medical
state: Texas
city: Tyler
country: United States
facility: Christus Trinity Mother Frances Health System
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Richmond
country: United States
facility: Chippenham & Johnston-Willis Hospital (CJW)
state: Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital-Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Graz
country: Austria
facility: Medizinische Univ.-Kliniken Graz-Hospital
city: Brugge
country: Belgium
facility: St. Jan
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Québec
country: Canada
facility: Institut universitaire de Cardiologie et de Pneumologie de Quebec
state: Quebec
city: Split
country: Croatia
facility: Klinicki Bolnicki Centar Split
city: Clermont-Ferrand
country: France
facility: CHRU de Clermont-Ferrand
city: Grenoble Cedex
country: France
facility: CHU Grenoble - Hopital Michallon
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum Bethanien
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Ancona
country: Italy
facility: AOU delle Marche - PO GM Lancisi
state: AN
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
state: MI
city: Cotignola
country: Italy
facility: Maria Cecilia Hospital SPA
state: RA
city: Roma
country: Italy
facility: Fondazione PTV - Policlinico Tor Vergata
city: Singapore
country: Singapore
facility: National Heart Centre Singapore
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital-Hospital
Study officials:
affiliation: The Cleveland Clinic
name: Oussama Wazni, M.D.
role: PRINCIPAL_INVESTIGATOR
References: