Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF (PULSED AF)

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia
      • John Hunter Hospital
• Austria
  • Linz, Austria, 4010
    • Ordensklinikum Linz GmbH / Elisabethinen
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge-Oostende AV
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Vancouver General Hospital
  • Ontario
    • Newmarket, Ontario, Canada
      • Southlake Regional Health Centre
  • Quebec
    • Montréal, Quebec, Canada, H3G1A4
      • McGill University Health Centre
    • Québec City, Quebec, Canada, G1V4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
• France
  • Neuilly-sur-Seine, France, 92200
    • CMC - Clinique Ambroise Paré
• Japan
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8563
      • Hirosaki University Hospital
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Tokyo
    • Bunkyō-Ku, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University, Medical Hospital
    • Minato-Ku, Tokyo, Japan, 105-8471
      • Jikei University
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Medical Center
  • Colorado
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Tampa, Florida, United States, 33607
      • BayCare Saint Joseph's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Saint Joseph's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iowa Heart Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Southcoast Health System
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic (Rochester MN)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Mid America Heart Institute
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Manhasset, New York, United States, 11030
      • Northwell Health - North Shore University Hospital
    • New York, New York, United States, 10016
      • NYU Langone Health - Heart Rhythm Center
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Mission Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center- UPMC Presbyterian
  • Texas
    • Austin, Texas, United States, 78705
      • St. David's Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center Cherry Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pilot; First group of patients enrolled in the study.	Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System; Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.
Experimental: Pivotal - Roll-In; First patient treated by each physician in the pivotal phase.	Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System; Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.
Experimental: Pivotal - Paroxysmal AF; Non roll-in patients with paroxysmal AF (intermittent AF).	Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System; Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.
Experimental: Pivotal - Persistent AF; Non roll-in patients with persistent AF (AF that lasts longer than 7 days).	Device: Medtronic PulseSelect Pulsed Field Ablation (PFA) System; Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Number of Participants With at Least One Primary Safety Event	Primary safety events are: Within 6 months post-ablation: Pulmonary vein stenosis (≥70% diameter reduction); Phrenic nerve injury/diaphragmatic paralysis (ongoing at 6 months); Atrioesophageal fistula Within 30 days of ablation procedure: Cardiac tamponade/perforation; Cerebrovascular accident; Major bleeding requiring transfusion; Myocardial infarction; Pericarditis requiring intervention; Transient ischemic attack; Vagal nerve injury resulting in esophageal dysmotility or gastroparesis; Vascular access complications requiring intervention; Systemic/pulmonary embolism requiring intervention; Pulmonary edema; Death; Any PulseSelect PFA System-related or PFA procedure-related cardiovascular and/or pulmonary adverse event that prolongs or requires hospitalization for more than 48 hours (excluding recurrent AF/AFL/AT)	up to 6 months
Effectiveness: Number of Participants With Treatment Success.	Treatment success is defined as freedom from treatment failure. The study requires 24-hour Holter monitoring at 6 and 12 months in addition to weekly and symptomatic patient activated ambulatory monitoring transmissions through 12 months, and 12-lead ECGs at all follow up visits. Treatment failure is defined as any of the following components: Acute procedural failure; Documented AF/AT/AFL on Holter/patient activated ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period.; Any subsequent AF surgery or ablation in the left atrium, except for one repeat PVI ablation using PFA within the 90-day blanking period.; Direct current cardioversion for atrial tachyarrhythmia recurrences after the 90-day blanking period.; Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90-day blanking period.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life - Change in EQ-5D Score	Change in EQ-5D score (12-month score - baseline score). The Euroqol EQ-5D questionnaire (5L version) is a standardized instrument for measuring general health status. The Euroqol EQ-5D questionnaire (which consists of a 5-question survey and a visual analog scale) has a composite score based on the 5-question survey that ranges from 0 (least healthy) to 1 (most healthy).	Baseline to 12 months post-ablation
Quality of Life - Change in AFEQT Score	Change in AFEQT score (12-month score - baseline score). The AFEQT questionnaire is an atrial fibrillation (AF) specific health-related quality of life questionnaire to assess the impact of AF on a subject's life. The overall score ranges from 0 - 100, with 0 corresponding to complete disability and 100 corresponding to no disability	Baseline to 12 months post-ablation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pilot Phase Safety: Number of Participants With a PFA System-related and PFA Procedure-related Serious Adverse Event (SAE) Within 30 Days Post-ablation.	Serious adverse events that count toward the endpoint are: Pulmonary vein stenosis (>70% diameter reduction) Atrioesophageal fistula Cardiac tamponade/perforation Cerebrovascular accident Major bleeding requiring transfusion Myocardial infarction Pericarditis requiring intervention Transient ischemic attack Vagal nerve injury resulting in esophageal dysmotility or gastroparesis Vascular access complications requiring intervention Systemic/pulmonary embolism requiring intervention Pulmonary edema Death	30 days
Pilot Phase Effectiveness: Number of Participants With Acute Procedural Success of PVI Ablation With the PFA System.	Acute procedural failure is defined as the occurrence of any of the following: Inability to isolate all accessible targeted pulmonary veins (assessed for entrance block and, where assessable, exit block) during the index ablation procedure.; Ablation using a non-study device in the left atrium. Acute procedural success is the opposite of acute procedural failure.	Acute (day of procedure)

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: Atul Verma, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): November 28, 2022
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 11, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: PULSED AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes