Clinical trial NCT04198701: Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF
Official title: Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: Medtronic Cardiac Ablation Solutions
Sponsor class: INDUSTRY
First posted: 2019-12-13
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study begins with a Pilot Phase, followed sequentially by a Pivotal Phase consisting of 3 arms enrolling simultaneously: Roll-in, Paroxysmal AF, Persistent AF
Primary purpose: TREATMENT

Brief summary: The study is a prospective, multi-center, non-randomized, unblinded worldwide pre-market clinical study. The purpose of the study is to provide data demonstrating the safety and effectiveness of the PulseSelect™ PFA System for the treatment of atrial fibrillation (AF). The study will also provide first in human insights into clinical safety and device function of the PulseSelect PFA System for pulmonary vein isolation (PVI) as a treatment for AF. To this end, the clinical study has been designed into phases (Pilot and Pivotal), with each phase comprising a separate data set that will be analyzed and reported on per the below objectives.


Eligibility criteria: Inclusion Criteria:

1. Failure of at least one AAD (class I or III) for AF as evidenced by recurrent symptomatic AF, or intolerable side effects due to AAD.
2. A diagnosis of recurrent symptomatic paroxysmal or persistent AF:

   1. Symptomatic paroxysmal AF, which is defined as AF that terminates spontaneously or with intervention within 7 days of onset, documented by the following:

      1. physician's note indicating at least 2 symptomatic paroxysmal AF episodes occurring within 6 months prior to enrollment; and
      2. at least 1 ECG documented AF episode from any form of rhythm monitoring within 12 months prior to enrollment OR
   2. Symptomatic persistent AF, which is defined as continuous AF sustained beyond 7 days and less than 1 year, documented by the following:

      1. physician's note indicating at least 1 symptomatic persistent AF episode occurring within 6 months prior to enrollment; and
      2. any 24-hour continuous ECG recording documenting continuous AF within 6 months prior to enrollment; OR 2 ECGs from any form of rhythm monitoring taken at least 7 days apart, both showing continuous AF within 6 months prior to enrollment
3. Age 18 through 80 years old (or older than 18 if required by local law)

Exclusion Criteria:

1. Long-standing persistent AF (continuous AF that is sustained \>12 months)
2. Left atrial diameter \> 5.0 cm (anteroposterior)
3. Prior left atrial ablation or surgical procedure (including left atrial appendage closures)
4. Planned LAA closure procedure or implant of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) for any time during the follow-up period
5. Patient who is not on oral anticoagulation therapy for at least 3 weeks prior to the ablation procedure
6. Presence of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function)
7. Presence of any pulmonary vein stents
8. Presence of any pre-existing pulmonary vein stenosis
9. Pre-existing hemidiaphragmatic paralysis
10. Presence of any cardiac valve prosthesis
11. Moderate to severe mitral valve stenosis
12. More than moderate mitral regurgitation (i.e., 3+ or 4+ MR)
13. Any cardiac surgery, myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3-month interval preceding the consent date
14. Unstable angina
15. NYHA Class III or IV congestive heart failure or documented left ventricular ejection fraction (LVEF) less than or equal to 35% measure by acceptable cardiac testing (e.g. TTE)
16. Primary pulmonary hypertension
17. Rheumatic heart disease
18. Thrombocytosis, thrombocytopenia
19. Any condition contraindicating chronic anticoagulation
20. Active systemic infection
21. Hypertrophic cardiomyopathy
22. Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, severe untreated obstructive sleep apnea, and acute alcohol toxicity
23. Any cerebral ischemic event (strokes or TIAs) which occurred during the 6-month interval preceding the consent date
24. History of thromboembolic event within the past 6 months or evidence of intracardiac thrombus at the time of the procedure
25. Any woman known to be pregnant or breastfeeding, or any woman of childbearing potential who is not on a reliable form of birth regulation method or abstinence
26. Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed
27. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic
28. Known allergies or hypersensitivities to adhesives
29. Unwilling or unable to comply fully with study procedures and follow-up
30. Unable to provide own informed consent

Primary outcomes:
measure: Safety: Number of Participants With at Least One Primary Safety Event
timeFrame: up to 6 months
measure: Effectiveness: Number of Participants With Treatment Success.
timeFrame: up to 12 months
Secondary outcomes:
measure: Quality of Life - Change in EQ-5D Score
timeFrame: Baseline to 12 months post-ablation
measure: Quality of Life - Change in AFEQT Score
timeFrame: Baseline to 12 months post-ablation
Other outcomes:
measure: Pilot Phase Safety: Number of Participants With a PFA System-related and PFA Procedure-related Serious Adverse Event (SAE) Within 30 Days Post-ablation.
timeFrame: 30 days
measure: Pilot Phase Effectiveness: Number of Participants With Acute Procedural Success of PVI Ablation With the PFA System.
timeFrame: Acute (day of procedure)
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Center
state: Alabama
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Tampa
country: United States
facility: BayCare Saint Joseph's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Hospital
state: Illinois
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Fall River
country: United States
facility: Southcoast Health System
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic (Rochester MN)
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Mid America Heart Institute
state: Missouri
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health - North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health - Heart Rhythm Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Doylestown
country: United States
facility: Doylestown Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center- UPMC Presbyterian
state: Pennsylvania
city: Austin
country: United States
facility: St. David's Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center Cherry Hill
state: Washington
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH / Elisabethinen
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende av
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Québec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
state: Quebec
city: Neuilly-sur-Seine
country: France
facility: CMC - Clinique Ambroise Paré
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Yoshida-gun
country: Japan
facility: University of Fukui Hospital
state: Fukui
city: Bunkyō-Ku
country: Japan
facility: Tokyo Medical and Dental University, Medical Hospital
state: Tokyo
city: Minato-Ku
country: Japan
facility: Jikei University
state: Tokyo
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Atul Verma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Verma A, Haines DE, Boersma LV, Sood N, Natale A, Marchlinski FE, Calkins H, Sanders P, Packer DL, Kuck KH, Hindricks G, Onal B, Cerkvenik J, Tada H, DeLurgio DB; PULSED AF Investigators. Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial. Circulation. 2023 May 9;147(19):1422-1432. doi: 10.1161/CIRCULATIONAHA.123.063988. Epub 2023 Mar 6.
citation: Verma A, Boersma L, Haines DE, Natale A, Marchlinski FE, Sanders P, Calkins H, Packer DL, Hummel J, Onal B, Rosen S, Kuck KH, Hindricks G, Wilsmore B. First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial. Circ Arrhythm Electrophysiol. 2022 Jan;15(1):e010168. doi: 10.1161/CIRCEP.121.010168. Epub 2021 Dec 29.