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

Paroxysmal Atrial Fibrillation Clinical Trial

— ADVENT  

Official title:

A Prospective Randomized Pivotal Trial of the FARAPULSE Pulsed Field Ablation System Compared With Standard of Care Ablation in Patients With Paroxysmal Atrial Fibrillation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04612244
• Other study ID #: CS0934
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: March 2024

Study information

• Verified date: January 2024
• Source: Farapulse, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 900
• Est. completion date: March 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key inclusion criteria: Patients are required to meet all the following inclusion criteria to participate in this study:

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.

Key exclusion criteria:

Patients will be excluded from participating in this study if they meet any one of the following exclusion criteria:

• 1. AF that is any of the following:

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Paroxysmal Atrial Fibrillation

Intervention

Device:
• FARAPULSE Pulsed Field Ablation System
Ablation using the FARAPULSE Pulsed Field Ablation System
• RadioFrequency and Cryoballoon Ablation
Contact Force Enabled RF and Cryoballoon ablation catheters indicated for Paroxysmal Atrial Fibrillation

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	St Davids_Texas Cardiac Arrhythmia Research Foundation	Austin	Texas
United States	Johns Hopkins	Baltimore	Maryland
United States	Grandview Medical Center	Birmingham	Alabama
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	St Luke's Regional Medical Center	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Trident Medical Center	Charleston	South Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Doylestown Hospital	Doylestown	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center/Hackensack Meridian Health	Hackensack	New Jersey
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	Catholic Medical Center	Manchester	New Hampshire
United States	Saint Thomas Heart at Baptist Hospital	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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	NYU Langone Health_Heart Rhythm Center	New York	New York
United States	MedStar Washington Hospital Center	Northwest	Washington
United States	Nebraska Methodist Health system, Inc	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Banner University Medical Center	Phoenix	Arizona
United States	Providence St Vincent Medical Center, Heart and Vascular Clinical Trials	Portland	Oregon
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	California Pacific Medical Center	San Francisco	California
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	HonorHealth Scottsdale Shea	Scottsdale	Arizona
United States	Swedish Medical Center Heart & Vascular Research	Seattle	Washington
United States	UPMC Pinnacle Health Cardiovascular Institute Inc.	Wormleysburg	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Farapulse, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Safety Endpoint;Proportion of Intent to Treat Subjects with one or more of the specified device or procedure related SAEs	Proportion of Intent to Treat subjects with one or more of the specified device or procedure related SAEs	7 days and 12 Months
Primary	Treatment success	Acute procedural success and Chronic success	12 Months
Primary	Primary Effectiveness Endpoint	Treatment Success: The primary effectiveness endpoint is Treatment Success in MITT Subjects, defined as: Acute Procedural Success AND; Chronic Success, defined as freedom from: At the Index / Rescheduled Index Procedure: Use of a non-randomized treatment modality for PVI; After the Blanking Period: i. Occurrence of any Detectable AF, AFL or AT (excluding CTI-dependent flutter confirmed by EP study); ii. Any cardioversion for AF, AFL or AT (excluding for CTI-dependent flutter); iii. Use of any Type I or Type III antiarrhythmic medication for the treatment of AF, AFL or AT; c. At any time: i. Re-ablation for AF, AFL or AT (other than for CTI-dependent flutter); ii. Use of amiodarone, except intra-procedurally to control an arrhythmia Endpoint status will be assessed through the Month 12 Assessment (Day 360 ± 30).	12-Months
Secondary	PV Diameter change	Change in pulmonary vein diameter	3 months
Secondary	Treatment Superiority	Treatment Success tested for superiority between the Pulsed Field and Thermal Groups.	12 Months
Secondary	Secondary Effectiveness Endpoint	The secondary effectiveness endpoint is the same as the primary effectiveness endpoint but will be tested for superiority rather than non-inferiority. The proportion of Pulsed Field Subjects with Treatment Success will be assessed for superiority to the proportion of Thermal Subjects with Treatment Success.	12 Months

External Links

•   Publication of ADVENT results (PubMed)