Pulsed Field Ablation Versus Conventional Radiofrequency Catheter Ablation for Repeat PVI in Patients With Paroxysmal AF (REPEAT-AF)

Pulsed Field Ablation Versus Conventional Radiofrequency Catheter Ablation for Repeat

Various methods exist for performing pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), including thermal ablation and pulse-field ablation (PFA). However, in cases requiring a second PVI for recurrent AF, radiofrequency ablation (RFA) is utilized in nearly 95% of instances post-acquiring a 3D high-density map from the left atrium (LA). Up to 85% of patients experiencing recurrent AF after the initial PVI exhibit pulmonary vein (PV) reconnections, often identified as the cause of AF.

PFA has demonstrated its safety and efficiency compared to RFA as a swift technique for performing ablation. Yet, whether PFA or RFA stands out as superior or safer when applied for a second PVI remains unclear, as no randomized controlled trial has investigated this comparison. The proposed REPEAT-AF trial aims to randomize 154 AF patients experiencing recurrent AF after the initial PVI, assigning them in a 1:1 ratio to either RFA or PFA. Each patient will receive an implantable cardiac monitor to precisely detect any AF recurrences.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation Recurrent
• Intervention / Treatment: Device: pulmonary vein isolation with RFA; Device: pulmonary vein isolation with PFA

Detailed Description

All participating patients are required to provide written (or equivalent) informed consent, indicated by a dated signature of the subject or legal representative. The consent process must comply with applicable national regulations and use language understandable by the patient.

The study will be conducted at 6 clinical centres/investigational sites across the Netherlands. Patients will be randomized (1:1) into a PFA or point-by-point RF ablation arm. Randomization will occur prior to the ablation procedure. A implantable cardiac monitor will be implanted in all randomised patients one month before ablation to accurately monitor any AF/atrial flutter (AFL)/ atrial tachycardia (AT) recurrence. Treatment allocation will be processed through the Dutch 'National Heart Registry' (NHR) data platform.

Patients randomized to both arms of the study will be evaluated for PV isolation at the start of the ablation procedure. If PV reconnection is identified in patients in the point-by-point RF arm, re-ablation will occur according to the study protocol. Patients in the PFA arm will have PV reconnection determined using the FARAWAVE catheter. Those with no PV reconnection (100% PV isolation/durable PVI) will be followed in an observational registry.

The PFA ablation arm involves the use of the Farastar generator system, Farawave ablation catheter, and Faradrive steering catheter for the procedure. The RF point-by-point ablation arm (control) involves RF ablation following standard practice.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuri Blaauw, Dr.; Phone Number: +31503616161; Email: y.blaauw01@umcg.nl
• Study Contact Backup: Name: Nick van Vreeswijk, drs.; Phone Number: +31503616161; Email: n.l.van.vreeswijk@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • UMCG
    • Contact: Yuri Blaauw, MD, PhD; Phone Number: 0503616161; Email: y.blaauw01@umcg.nl
    • Contact: Nick van Vreeswijk, MD; Phone Number: 0503616161; Email: n.l.van.vreeswijk@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Subjects who meet all of the following inclusion criteria at screening will be eligible for enrolment:

• Patient had 1 previous PVI with either cryoballoon, RF ablation or PFA
• Index PVI occurred within <5 years prior to enrolment
• Documented AF recurrence >30 seconds
• Symptomatic AF
• Paroxysmal AF
• Age >18 and <80 years
• Willing and capable to provide informed consent
• Able and willing to participate in all examinations and follow-up visits and tests associated with this clinical study

Subjects who meet ANY of the following exclusion criteria will be excluded from the study:

• Persistent AF (by diagnosis of duration >7 days)
• Concomitant/ prior diagnosis for atrial tachycardia (AT) and/or atrial flutter (AFl). Note typical cavotricuspid isthmus dependent flutter is not an exclusion criterium.
• Underwent additional ablations outside the pulmonary veins during index AF ablation
• AF secondary to electrolyte imbalance, thyroid disease, alcohol abuse, or other reversible/non-cardiac causes
• Contraindication to, or unwillingness to use, systematic anticoagulation
• Left ventricular ejection fraction (LVEF) <30% as documented by transthoracic echo (TTE) (within <3 months prior)
• Left atrial volume index >60 ml/m2
• Clinically significant arrhythmias other than AF
• Previous surgery for AF
• New York Heart Association (NYHA) Functional Class III or IV
• Presence of intramural thrombus, tumour or other abnormality that precludes safe catheter introduction or manipulation
• BMI >35 kg/m2
• Significant or symptomatic hypotension, bradycardia, or chronotropic incompetence
• Chronic renal insufficiency of <15 mL/min/1.73 m2 or any history of renal dialysis, or history of renal transplant
• Hemodynamically significant valvular disease
• Presence of patent foramen ovale (PFO) or atrial septal defect (ASD) closure device
• History of abnormal bleeding and/or clotting disorder
• History of rheumatic fever
• Severe lung disease, pulmonary hypertension, or any lung disease. Only if involving abnormal blood gases or significant dyspnoea
• Clinically significant systemic infection or sepsis
• Life expectancy <1 year
• Sensitivity to contrast media not controlled by pre-medication

• Any of the following within the 3 months prior to enrolment:

  • Myocardial infarction
  • Unstable angina
  • Percutaneous coronary intervention
  • Heart failure hospitalization
  • Stroke or TIA
  • Significant bleeding
  • Pericarditis/effusions
  • Left atrial thrombus
• Coronary artery bypass grafting/atriotomy within 6 months prior
• Organ or haematologic transplant, or currently being evaluated for an organ transplant
• Women who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiofrequency ablation; In this group, patients will undergo the acquisition of a 3D high-density map. If pulmonary vein (PV) reconnection is identified, radiofrequency ablation (RFA) will be employed for pulmonary vein isolation (PVI). Should PV reconnection not be detected, the operator will have the discretion to determine the necessary ablation strategies. Patients falling into this category will be included in a concurrent registry.	Device: pulmonary vein isolation with RFA; Patients randomised to RFA will undergo PVI with point-by-point RFA.
Experimental: Pulsed field ablation; In this group, pulmonary vein (PV) reconnection is identified by the FARAWAVE system. If reconnection is observed, pulsed field ablation (PFA) will be employed for pulmonary vein isolation (PVI). Should PV reconnection not be detected, the operator will have the discretion to determine the necessary ablation strategies. Patients falling into this category will be included in a concurrent registry.	Device: pulmonary vein isolation with PFA; Patients randomised to PFA will undergo PVI with PFA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the efficacy of repeat pulmonary vein isolation (PVI) with PFA or point-by-point RF ablation.	12-month incidence of AF/AFl/AT recurrence.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the efficacy of repeat pulmonary vein isolation (PVI) with PFA or point-by-point RF ablation.	24-month incidence of AF/AFl/AT recurrence.	24 months
Repeat PVI within 12 and 24 months of randomization	Repeat PVI	12 and 24 months
AF burden with and without 3 months blanking period	Proportion of cumulative time in AF divided by the total time accrued over follow-up	12 and 24 months
AF hospitalisation / urgent visit	Hospitalization/urgent visit for atrial fibrillation	12 and 24 months
Change in quality of life	As measured by EuroQol-5D-5L questionnaire	12 and 24 months
Change in quality of life as affected by AF	As measured by AF Effect On Quality-Of-Life (AFEQT) questionnaire	12 and 24 months
Cost-effectiveness	Cost-effectiveness	12 and 24 months
Rate of ischemic stroke	Rate of ischemic stroke	12 and 24 months (efficacy)
Complications of ablation	Death, stroke, pericarditis, cardiac tamponade, vascular access complications etc.	0-30 days post ablation

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Yuri Blaauw, Dr., UMCG

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: December 1, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: radiofrequency ablation; pulmonary vein isolation; implantable cardiac monitor; pulsed field ablation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: REPEAT-AF trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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