The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation

NCT ID: NCT04612244

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 706 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2023-05-15

Brief Summary

This is a prospective, adaptive, multi-center, randomized safety and effectiveness pivotal study comparing the FARAPULSE Pulsed Field Ablation System with standard of care ablation with force-sensing RF catheters and cryoballoon catheters indicated for the treatment of PAF.

Conditions

Paroxysmal Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

FARAPULSE Pulsed Field Ablation System

Group Type: EXPERIMENTAL

FARAPULSE Pulsed Field Ablation System

Intervention Type: DEVICE

Ablation using the FARAPULSE Pulsed Field Ablation System

Force Sensing Radiofrequency Ablation and Cryoballoon Ablation

Group Type: ACTIVE_COMPARATOR

RadioFrequency and Cryoballoon Ablation

Intervention Type: DEVICE

Contact Force Enabled RF and Cryoballoon ablation catheters indicated for Paroxysmal Atrial Fibrillation

Interventions

FARAPULSE Pulsed Field Ablation System

Ablation using the FARAPULSE Pulsed Field Ablation System

Intervention Type: DEVICE

RadioFrequency and Cryoballoon Ablation

Contact Force Enabled RF and Cryoballoon ablation catheters indicated for Paroxysmal Atrial Fibrillation

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Patients with drug-resistant symptomatic PAF meeting all the following criteria:

a. Paroxysmal: AF that terminates spontaneously or with intervention within 7 days of onset.

b. Frequency: i. Physician documentation of recurrent PAF (two or more episodes) within 6 months, AND

ii. At least one (1) documented episode by a recording such as ECG, EM, Holter monitor or telemetry strip within 12 months of enrollment.

c. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least one (1) AAD (Class I to IV) for efficacy and / or intolerance.

2. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment.

3. Patient who are willing and capable of:

1. Providing informed consent to undergo study procedures AND

2. Participating in all examinations and follow-up visits and tests associated with this clinical study.

Exclusion Criteria

• 1. AF that is any of the following:

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1. Persistent (both early and longstanding) by diagnosis or continuous duration > 7 days

2. Requires four (4) or more direct-current cardioversions in the preceding 12 months

3. Secondary to electrolyte imbalance, thyroid disease, alcohol or other reversible / non-cardiac causes

2. Any of the following atrial conditions:

1. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT or TTE)

2. Any prior atrial endocardial or epicardial ablation procedure, other than right sided cavotricuspid isthmus ablation or for right sided SVT

3. Any prior atrial surgery

4. Intra-atrial septal patch or interatrial shunt

5. Atrial myxoma

6. Current LA thrombus

7. LA appendage closure, device or occlusion, past or anticipated

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

3. At any time, one (1) or more of the following cardiovascular procedures, implants or conditions:

a. Sustained ventricular tachycardia or any ventricular fibrillation

b. Hemodynamically significant valvular disease:

i. Valvular disease that is symptomatic

ii. Valvular disease causing or exacerbating congestive heart failure

iii. Aortic stenosis: if already characterized, valve area < 1.5cm or gradient > 20 mm Hg

iv. Mitral stenosis: if already characterized, valve area < 1.5cm or gradient > 5 mm Hg

v. Aortic or mitral regurgitation associated with abnormal LV function or hemodynamic measurements

c. Hypertrophic cardiomyopathy

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

e. Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices

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

g. History of rheumatic fever

h. History of congenital heart disease with any residual anatomic or conduction abnormality

4. Any of the following procedures, implants or conditions:

1. At baseline:

i. New York Heart Association (NYHA) Class III/IV

ii. Left ventricular ejection fraction (LVEF) < 40%

iii. Symptomatic hypotension

iv. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two BP measurements at baseline assessment)

v. Symptomatic resting bradycardia

vi. Implantable loop recorder or insertable cardiac monitor,

b. Within the 3 months preceding the Consent Date:

i. Myocardial infarction

ii. Unstable angina

iii. Percutaneous coronary intervention

iv. Heart failure hospitalization

v. Treatment with amiodarone

vi. Pericarditis or symptomatic pericardial effusion

vii. Gastrointestinal bleeding

c. Within the 6 months preceding the Consent Date:

i. Heart surgery

ii. Stroke, TIA or intracranial bleeding

iii. Any thromboembolic event

iv. Carotid stenting or endarterectomy

5. Diagnosed disorder of blood clotting or bleeding diathesis

6. Contraindication to, or unwillingness to use, systemic anticoagulation

7. Patient who is not on anticoagulation therapy for at least 3 weeks prior to the ablation procedure

8. Contraindication to both CT and MRI

9. Sensitivity to contrast media not controllable by premedication

10. 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

11. Medical conditions that 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) > 40.0

2. Solid organ or hematologic transplant, or currently being evaluated for an organ transplant

3. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen

4. Renal insufficiency with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant

5. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)

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

7. Active systemic infection

8. COVID-19 disease

9. 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.

i. Other uncontrolled medical conditions that may modify device effect or increase risk, including uncontrolled diabetes mellitus (HgbA1c > 8.0% if test result already obtained) or active alcohol abuse

j. Sleep apnea and:

i. An apnea-hypopnea index (AHI) ≥ 15, or

ii. An AHI of ≥ 5 and ≤14 with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease or history of stroke, unless compliant with continuous positive airway pressure (CPAP) treatment.

k. Predicted life expectancy less than one (1) year

12. Clinically significant psychological condition that in the Investigator's opinion would prohibit the subject's ability to meet the protocol requirements

13. Current or anticipated enrollment in any other randomized, interventional or Food and Drug Administration (FDA)-regulated clinical study (data collection for registries or retrospective studies is permitted)

14. Employees / family members of:

1. FARAPULSE or any of its affiliates or contractors

2. The Investigator, sub-Investigators, or their medical office or practice, or healthcare organizations at which study procedures may be performed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Scientific Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vivek Reddy, MD

Role: PRINCIPAL_INVESTIGATOR

Mt. Sinai

Locations

Grandview Medical Center

Birmingham, Alabama, United States

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner University Medical Center

Phoenix, Arizona, United States

HonorHealth Scottsdale Shea

Scottsdale, Arizona, United States

Scripps Memorial Hospital La Jolla

La Jolla, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of California San Francisco (UCSF)

San Francisco, California, United States

Emory University Hospital

Atlanta, Georgia, United States

St Luke's Regional Medical Center

Boise, Idaho, United States

Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital (MGH)

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Nebraska Methodist Health system, Inc

Omaha, Nebraska, United States

Catholic Medical Center

Manchester, New Hampshire, United States

Hackensack University Medical Center/Hackensack Meridian Health

Hackensack, New Jersey, United States

NYU Langone Health_Heart Rhythm Center

New York, New York, United States

Mount Sinai, Icahn School of Medicine

New York, New York, United States

Northwell Health- Lenox Hill Hospital

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Providence St Vincent Medical Center, Heart and Vascular Clinical Trials

Portland, Oregon, United States

Doylestown Hospital

Doylestown, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

UPMC Pinnacle Health Cardiovascular Institute Inc.

Wormleysburg, Pennsylvania, United States

Trident Medical Center

Charleston, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Saint Thomas Heart at Baptist Hospital

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

St Davids_Texas Cardiac Arrhythmia Research Foundation

Austin, Texas, United States

University of Virginia Medical Center

Charlottesville, Virginia, United States

Virginia Commonwealth University Health System

Richmond, Virginia, United States

MedStar Washington Hospital Center

Northwest, Washington, United States

Swedish Medical Center Heart & Vascular Research

Seattle, Washington, United States

Countries

United States

References

Reddy VY, Mansour M, Calkins H, d'Avila A, Chinitz L, Woods C, Gupta SK, Kim J, Eldadah ZA, Pickett RA, Winterfield J, Su WW, Waks JW, Schneider CW, Richards E, Albrecht EM, Sutton BS, Gerstenfeld EP; ADVENT Investigators. Pulsed Field vs Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: Recurrent Atrial Arrhythmia Burden. J Am Coll Cardiol. 2024 Jul 2;84(1):61-74. doi: 10.1016/j.jacc.2024.05.001. Epub 2024 May 18.

Reference Type: DERIVED

PMID: 38864538 (View on PubMed)

Reddy VY, Gerstenfeld EP, Natale A, Whang W, Cuoco FA, Patel C, Mountantonakis SE, Gibson DN, Harding JD, Ellis CR, Ellenbogen KA, DeLurgio DB, Osorio J, Achyutha AB, Schneider CW, Mugglin AS, Albrecht EM, Stein KM, Lehmann JW, Mansour M; ADVENT Investigators. Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2023 Nov 2;389(18):1660-1671. doi: 10.1056/NEJMoa2307291. Epub 2023 Aug 27.

Reference Type: DERIVED

PMID: 37634148 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/37634148/

Publication of ADVENT results (PubMed)

Other Identifiers

CS0934

Identifier Type: -

Identifier Source: org_study_id