Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF

Atrial Fibrillation Clinical Trial

— PULSED AF  

Official title:

Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04198701
• Other study ID #: PULSED AF
• Status: Completed
• Phase: N/A
• Start date: December 10, 2019
• Est. completion date: November 28, 2022

Study information

• Verified date: January 2024
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 421
• Est. completion date: November 28, 2022
• Est. primary completion date: November 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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.

Locations

Country	Name	City	State
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Austria	Ordensklinikum Linz GmbH / Elisabethinen	Linz
Belgium	AZ Sint-Jan Brugge-Oostende av	Brugge
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)	Québec City	Quebec
Canada	Vancouver General Hospital	Vancouver	British Columbia
France	CMC - Clinique Ambroise Paré	Neuilly-sur-Seine
Japan	Tokyo Medical and Dental University, Medical Hospital	Bunkyo-Ku	Tokyo
Japan	Hirosaki University Hospital	Hirosaki	Aomori
Japan	Jikei University	Minato-Ku	Tokyo
Japan	University of Fukui Hospital	Yoshida-gun	Fukui
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
Spain	Hospital General Universitario Gregorio Marañón	Madrid
United States	Mission Hospital	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	St. David's Medical Center	Austin	Texas
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Grandview Medical Center	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Northwestern University Hospital	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Iowa Heart Center	Des Moines	Iowa
United States	Doylestown Hospital	Doylestown	Pennsylvania
United States	Southcoast Health System	Fall River	Massachusetts
United States	Spectrum Health	Grand Rapids	Michigan
United States	Saint Luke's Mid America Heart Institute	Kansas City	Missouri
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Northwell Health - North Shore University Hospital	Manhasset	New York
United States	NYU Langone Health - Heart Rhythm Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center- UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Mayo Clinic (Rochester MN)	Rochester	Minnesota
United States	Beaumont Hospital	Royal Oak	Michigan
United States	Swedish Medical Center Cherry Hill	Seattle	Washington
United States	BayCare Saint Joseph's Hospital	Tampa	Florida
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Japan,  Netherlands,  Spain, 

References & Publications (2)

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 — View 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: PUL — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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)
Primary	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
Primary	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	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
Secondary	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