A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE) (inspIRE)

• ClinicalTrials.gov Identifier: NCT04524364
• Recruitment Status: Completed
• First Posted: August 24, 2020
• Results First Posted: May 14, 2024
• Last Update Posted: May 14, 2024
• Sponsor: Biosense Webster, Inc.
• Information provided by (Responsible Party): Biosense Webster, Inc.

Tracking Information

• First Submitted Date: August 18, 2020
• First Posted Date: August 24, 2020
• Results First Submitted Date: April 17, 2024
• Results First Posted Date: May 14, 2024
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: August 23, 2020
• Actual Primary Completion Date: May 9, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2024)

• Number of Participants With Primary Adverse Events (PAEs) [ Time Frame: Within 7 days post-procedure on Day 0 ]
  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).
• 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 [ Time Frame: 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 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.

Original Primary Outcome Measures (submitted: August 21, 2020)

• Number of Participants with of Primary Adverse Events (PAEs) [ Time Frame: Within one week (7 days) post-procedure ]
  Participants with incidence of Primary Adverse Events (PAEs) (within seven (7) days of the initial mapping and ablation procedure) will be reported. PAEs include the adverse events like Atrio-esophageal fistula, cardiac tamponade/perforation, device or procedure related death, major vascular access complication/bleeding, myocardial infarction and pericarditis, phrenic nerve paralysis (permanent), pulmonary vein stenosis, stroke/CVA, thromboembolism, transient Ischemic Attack (TIA)
• Rate of Freedom from Documented (Symptomatic and Asymptomatic) Atrial Arrhythmia (Atrial Fibrillation [AF], Atrial Tachycardia [AT], or Atrial Flutter [AFL] Greater than Equal to (>=)30 Seconds Within 91-365 days post Index Procedure [ Time Frame: 91-365 Days ]
  Atrial arrhythmia recurrence events will be recorded and included as a study endpoint after a 90-day blanking period; recurrence during the blanking will not be considered treatment failure. In addition, re-ablation will not be recommended during the blanking period.

Current Secondary Outcome Measures (submitted: April 17, 2024)

• Number of Participants Who Achieved Acute Procedural Success [ Time Frame: 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.
• 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 [ Time Frame: 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.
• Change From Baseline in Atrial Fibrillation Effect on Quality of Life (AFEQT) Total Score [ Time Frame: Baseline, Months 3, 6, and 12 ]
  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).

Original Secondary Outcome Measures (submitted: August 21, 2020)

• Number of Participants who Achieved Acute Procedural Success [ Time Frame: 91-365 Days ]
  Acute procedural success defined as confirmation of entrance block in all clinically relevant targeted PVs after adenosine/ isoproterenol challenge.
• Rate of Freedom from Documented Symptomatic Re-Occurrence Atrial Arrhythmia (Atrial Fibrillation [AF], Atrial Tachycardia [AT], or Atrial Flutter [AFL]) >=30 Seconds Within 91-365 days post Index Procedure [ Time Frame: 91-365 Days ]
  Atrial arrhythmia recurrence events will be recorded and included as a study endpoint after a 90-day blanking period; recurrence during the blanking will not be considered treatment failure. In addition, re-ablation will not be recommended during the blanking period.
• Change from Baseline in Atrial Fibrillation Effect on Quality of Life (AFEQT) Total Score [ Time Frame: Baseline, Month 3, 6 and 12 ]
  An overall AFEQT score ranges from 0 to 100. A score of 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 AF symptoms.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE)
• Official Title: Pulsed Field Ablation (PFA) System for the Treatment of Paroxysmal Atrial Fibrillation (PAF) by Irreversible Electroporation (IRE)
• Brief Summary: The primary objective is to demonstrate safety and long-term effectiveness of the irreversible electroporation (IRE) system (Circular IRE Catheter and IRE Generator) when used for isolation of the atrial pulmonary veins (PVs) in treatment of participants with paroxysmal atrial fibrillation (PAF).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Atrial Fibrillation

Intervention

Device: Pulsed Field Ablation (PFA) Therapy

Participants will undergo PFA therapy with a compatible ablation catheter when used with Multi-Channel irreversible electroporation (IRE) Generator (deliver trains of high-voltage bipolar pulses of short duration on separate channels to a multi-electrode ablation catheter) and Circular IRE Catheter (indicated for use in catheter-based cardiac electrophysiological mapping (stimulating and recording) and, when used with an IRE Generator, for cardiac ablation).

Study Arms

Participants with Paroxysmal Atrial Fibrillation (PAF)

Participants with PAF and who are candidates for catheter ablation will be enrolled.

Intervention: Device: Pulsed Field Ablation (PFA) Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 28, 2023): 272
• Original Estimated Enrollment (submitted: August 21, 2020): 550
• Actual Study Completion Date: May 9, 2023
• Actual Primary Completion Date: May 9, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with Symptomatic paroxysmal atrial fibrillation (PAF)
• Selected for atrial fibrillation (AF) ablation procedure by pulmonary vein isolation (PVI)
• Failed at least one antiarrhythmic drug (AAD) (class I to IV) as evidenced by recurrent symptomatic atrial fibrillation AF, or intolerable or contraindicated to the AAD
• Willing and capable of providing consent
• Able and willing to comply with all pre-, post- and follow-up testing and requirements

Exclusion Criteria:

• AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause
• Previous left atrium (LA) ablation or surgery
• Participant known to require ablation outside the PV region (example. cavotricuspid isthmus [CTI] region, atrioventricular reentrant tachycardia, atrioventricular nodal reentry tachycardia, atrial tachycardia, ventricular tachycardia and Wolff-Parkinson-White)
• Previously diagnosed with persistent AF (greater than [>] 7 days in duration)
• Severe dilatation of the LA (LAD >50 millimeter (mm) antero-posterior diameter in case of transthoracic echocardiography (TTE))

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Croatia, Czechia, France, Italy, Lithuania

Administrative Information

• NCT Number: NCT04524364
• Other Study ID Numbers: BWI_2019_08; BWI_2019_08 ( Other Identifier: Biosense Webster, Inc. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Johnson & Johnson Medical Device Companies have an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for evaluation of requests for clinical study reports and participant level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Requests for access to the study data can be submitted through the YODA Project site at http://yoda.yale.edu.
• URL: http://yoda.yale.edu.

• Current Responsible Party: Biosense Webster, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Biosense Webster, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Biosense Webster, Inc.
• Verification Date: April 2024