Trial Outcomes & Findings for A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE) (NCT NCT04524364)

Last Updated: 2025-05-25

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. The primary safety endpoint was the incidence of PAEs (within 7 days of the initial mapping and ablation procedure). PAEs included the following AEs: Atrio-esophageal fistula, cardiac tamponade/perforation, device or procedure related death, major vascular access complication/bleeding, myocardial infarction, pericarditis, phrenic nerve paralysis (permanent), pulmonary vein stenosis, stroke/cerebrovascular accident (CVA), thromboembolism, and transient ischemic attack (TIA).

Recruitment status

COMPLETED

Study phase

Target enrollment

272 participants

Primary outcome timeframe

Within 7 days post-procedure on Day 0

Results posted on

2025-05-25

Participant Flow

Participant milestones

Participant milestones
Measure	Wave I Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II Participants were enrolled in Wave II (Wave II main phase or Wave II roll-in) and treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Overall Study STARTED	45	227
Overall Study Treated	40	216
Overall Study Wave II: Main Phase Full Analysis Set	0	186
Overall Study Wave II: Roll-in Analysis Set (RI AS)	0	30
Overall Study COMPLETED	40	216
Overall Study NOT COMPLETED	5	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Wave I Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II Participants were enrolled in Wave II (Wave II main phase or Wave II roll-in) and treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Overall Study Physician Decision	3	6
Overall Study Adverse Event	0	1
Overall Study Investigational device deficiency	0	1
Overall Study Implantable cardioverter device (ICD) discovered	0	1
Overall Study Device unavailability	0	2
Overall Study Atrio-ventricular Paroxysmal tachycardia requiring ablation outside PV	1	0
Overall Study Low International normalized ratio (INR)	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Wave I n=40 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=186 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=30 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Total n=256 Participants Total of all reporting groups
Age, Continuous	58.4 Years STANDARD_DEVIATION 10.86 • n=40 Participants	59.4 Years STANDARD_DEVIATION 10.18 • n=186 Participants	56.2 Years STANDARD_DEVIATION 11.72 • n=30 Participants	58.0 Years STANDARD_DEVIATION 10.92 • n=256 Participants
Sex: Female, Male Female	17 Participants n=40 Participants	55 Participants n=186 Participants	10 Participants n=30 Participants	82 Participants n=256 Participants
Sex: Female, Male Male	23 Participants n=40 Participants	131 Participants n=186 Participants	20 Participants n=30 Participants	174 Participants n=256 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Within 7 days post-procedure on Day 0

Population: Wave I and Wave II (Main Phase): The full analysis set (FAS) included all enrolled Wave I and Wave II (main phase) participants who had insertion of the study catheter (with or without delivery of pulse field ablation \[PFA\]); Wave II (Roll-in): The Roll-In analysis set (RI AS) included all Wave II (roll-in) participants who were enrolled in the roll-in phase and underwent ablation with the irreversible electroporation (IRE) ablation system.

Outcome measures

Outcome measures
Measure	Wave I n=40 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=186 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=30 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Number of Participants With Primary Adverse Events (PAEs)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Day 91 up to Day 365 post index procedure on Day 0

Population: Wave I and Wave II (Main Phase): The FAS included all enrolled Wave I and Wave II (main phase) participants who had insertion of the study catheter (with or without delivery of PFA); Wave II (Roll-in): The RI AS included all Wave II (roll-in) participants who were enrolled in the roll-in phase and underwent ablation with the IRE ablation system.

Kaplan-Meier estimates of the success rate of freedom from primary effectiveness failure, that is, documented (symptomatic and asymptomatic) atrial arrhythmia (AF, AT, or AFL) recurrence based on electrocardiographic data (\>=30 seconds on arrhythmia monitoring device) from Day 91 to Day 365 post index procedure, was reported. Acute procedural failure defined as failure to confirm entrance block in all PVs except those that are silent and/or cannot be cannulated post-procedure, use of a non-study catheter for PV isolation, or failure to have PFA delivery with the study catheter due to IRE system malfunctions, was also considered a long-term effectiveness failure.

Outcome measures

Outcome measures
Measure	Wave I n=40 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=186 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=30 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Kaplan-Meier Estimates of the Success Rate of Freedom From Documented (Symptomatic and Asymptomatic) Atrial Arrhythmia (Atrial Fibrillation [AF], Atrial Tachycardia [AT], or Atrial Flutter [AFL]) Episodes From Day 91 to Day 365 Post Index Procedure	71.8 Percentage of participants	75.6 Percentage of participants	80.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 0 (Day of procedure)

Number of participants who achieved acute procedural success were reported. Acute procedural success was defined as confirmation of entrance block in all clinically relevant targeted pulmonary veins (PVs) after adenosine/ isoproterenol challenge.

Outcome measures

Outcome measures
Measure	Wave I n=40 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=186 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=30 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Number of Participants Who Achieved Acute Procedural Success	40 Participants	186 Participants	30 Participants

SECONDARY outcome

Timeframe: From Day 91 up to Day 365 post index procedure on Day 0

Kaplan-Meier estimates of the success rate of freedom from primary effectiveness failure, that is, documented symptomatic re-occurrence of atrial arrhythmia (AF, AT, or AFL) episodes based on electrocardiographic data (\>=30 seconds on arrhythmia monitoring device) from Day 91 to Day 365 post index procedure, was reported. Acute procedural failure defined as failure to confirm entrance block in all PVs except those that are silent and/or cannot be cannulated post-procedure, use of a non-study catheter for PV isolation, or failure to have PFA delivery with the study catheter due to IRE system malfunctions, was also considered a long-term effectiveness failure.

Outcome measures

Outcome measures
Measure	Wave I n=40 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=186 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=30 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Kaplan-Meier Estimates of the Success Rate of Freedom From Documented Symptomatic Re-Occurrence of Atrial Arrhythmia (Atrial Fibrillation [AF], Atrial Tachycardia [AT], or Atrial Flutter [AFL]) Episodes From Day 91 to Day 365 Post Index Procedure	76.9 Percentage of participants	81.7 Percentage of participants	80.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, and 12

Population: The FAS included all enrolled Wave I and Wave II (main phase) participants who had insertion of the study catheter (with or without delivery of PFA). The RI AS included all Wave II (roll-in) participants who were enrolled in the roll-in phase and underwent ablation with the IRE ablation system. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified timepoints.

Change from baseline in AFEQT total score was reported. The AFEQT questionnaire is an atrial fibrillation-specific health-related quality of life (HRQoL) questionnaire designed to assess the impact of atrial fibrillation on participants' HRQoL. The questionnaire includes 20 questions on a 7-point Likert scale. Questions 1-18 evaluate HRQoL and questions 19-20 relate to participants' satisfaction with treatment. Overall or subscale scores range from 0 to 100, where 0 corresponds to complete disability (or responding "extremely" limited, difficult or bothersome to all questions answered), while a score of 100 corresponds to no disability (or responding "not at all" limited, difficult or bothersome to all questions answered). Therefore, a positive change in score corresponds to improvement in QoL. Total score was calculated using AFEQT formula: 100 -(\[sum of severity for all questions answered - number of questions answered\]\*100 / total number questions answered\*6).

Outcome measures

Outcome measures
Measure	Wave I n=35 Participants Participants with drug refractory, symptomatic pulse field ablation (PAF) who were candidates for catheter ablation, underwent the index procedure and additional neurological, pulmonary vein (PV) and esophageal assessments to obtain data for preliminary estimates of safety and (acute) effectiveness of the irreversible electroporation (IRE) ablation system.	Wave II: Main Phase n=182 Participants Participants enrolled in Wave II main phase, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.	Wave II: Roll-In n=24 Participants Participants enrolled in Wave II roll-in, were treated with the Circular IRE Catheter in conjunction with the IRE Generator.
Change From Baseline in Atrial Fibrillation Effect on Quality of Life (AFEQT) Total Score Month 3	27.38 Units on a score Standard Deviation 19.685	23.02 Units on a score Standard Deviation 22.755	26.03 Units on a score Standard Deviation 22.693
Change From Baseline in Atrial Fibrillation Effect on Quality of Life (AFEQT) Total Score Month 6	28.21 Units on a score Standard Deviation 16.422	25.06 Units on a score Standard Deviation 20.793	24.77 Units on a score Standard Deviation 23.414
Change From Baseline in Atrial Fibrillation Effect on Quality of Life (AFEQT) Total Score Month 12	30.5 Units on a score Standard Deviation 19.897	26.05 Units on a score Standard Deviation 21.642	31.17 Units on a score Standard Deviation 19.723

Adverse Events

Wave I

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Wave II: Main Phase

Serious events: 9 serious events

Other events: 85 other events

Deaths: 0 deaths

Wave II: Roll-In

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Associate Director - Medical Affairs

Biosense Webster, Inc.

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Authorship will be determined prior to development of any manuscript. All information concerning the study, investigational medical device, sponsor operations, patent application, manufacturing processes, and basic scientific data supplied by the sponsor to the investigator and not previously published, are considered confidential and remain the sole property of the sponsor.
Publication restrictions are in place

Restriction type: OTHER