Pulsed Field Ablation Versus Conventional Radiofrequency Catheter Ablation for Repeat PVI in Patients With Paroxysmal AF

Atrial Fibrillation Recurrent Clinical Trial

— REPEAT-AF  

Official title:

Pulsed Field Ablation Versus Conventional Radiofrequency Catheter Ablation for Repeat

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06199180
• Other study ID #: REPEAT-AF trial
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: July 2028

Study information

• Verified date: May 2024
• Source: University Medical Center Groningen
• Contact: Yuri Blaauw, Dr.
• Phone: +31503616161
• Email: y.blaauw01[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This study involves assessing suitable patients through (a) review of the patient's medical/surgical history, (b) assessment of concomitant medications, (c) documentation of AF recurrence ≥30 seconds, (d) transthoracic echocardiogram (≤6 months prior), and (e) an evaluation by the treating cardiac electrophysiologist to confirm eligibility for repeat PVI. Qualified screened patients are eligible for study enrolment.

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.

Patients will be closely monitored during the study for any adverse effects or procedure-related complications.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 154
• Est. completion date: July 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

• Patient had 1 previous PVI with either cryoballoon or RF ablation

• 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)

• Index AF ablation performed with PFA

• 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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation Recurrent

Intervention

Device:
• pulmonary vein isolation with RFA
Patients randomised to RFA will undergo PVI with point-by-point RFA.
• pulmonary vein isolation with PFA
Patients randomised to PFA will undergo PVI with PFA.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Boston Scientific Corporation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Freedom from AF/AFl/AT recurrence at 12- and 24-months follow-up	No blanking period	12 and 24 months
Secondary	Repeat PVI within 12 and 24 months of randomization	Repeat PVI	12 and 24 months
Secondary	Acute outcome: 100% PV isolation post PVI	100% PV isolation as assessed after PVI	peri procedural
Secondary	Anti-arrhythmic drug (AAD) therapy at 3, 6, 12, and 24 months	Use of anti-arrhythmic drugs	3, 6, 12, and 24 months
Secondary	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
Secondary	Delta AF burden with and without 3 months blanking period	AF burden prior to repeat AF ablation minus AF burden post AF ablation	12 and 24 months
Secondary	Quality of life	As measured by AF Effect On Quality-Of-Life (AFEQT) questionnaire	12 and 24 months
Secondary	Quality of life	As measured by EQ-5D-5L questionnaire	12 and 24 months
Secondary	Procedure time	Initiation of venous access to venous access closure	peri procedural
Secondary	Left atrial dwell time	Sum of catheter entry-to-exit durations for the left atrium	peri procedural
Secondary	Total ablation time	First ablation to last ablation	peri procedural
Secondary	Fluoroscopy time	Total duration of exposure	peri procedural
Secondary	Duration of hospitalization for PVI	Duration of hospitalization for PVI	peri procedural
Secondary	Progression to persistent AF	AF duration of =7 days	12 and 24 months
Secondary	Heart failure hospitalization	Hospitalization for heart failure	12 and 24 months
Secondary	AF hospitalisation / urgent visit	Hospitalization/urgent visit for atrial fibrillation	12 and 24 months
Secondary	Direct current cardioversion or intravenous cardioversion	Direct current cardioversion or intravenous cardioversion for AF/AFL/AT	12 and 24 months
Secondary	Quality adjusted life years (QALY)	Cost-effectiveness	12 and 24 months
Secondary	ischemic stroke	ischemic stroke	0-30 days (safety); 12 and 24 months (efficacy)
Secondary	Death	Death	0-30 days post ablation
Secondary	Myocardial infarction	Myocardial infarction	0-30 days post ablation
Secondary	Thrombo-embolic complication	Cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary/systemic embolism)	0-72 hours after PVI
Secondary	Major bleeding	Bleeding Academic Research Consortium (BARC) type =2	0-30 days post ablation
Secondary	Pericarditis	requiring intervention	0-30 days post ablation
Secondary	Cardiac tamponade/perforation	requiring intervention	0-30 days post ablation
Secondary	Vascular access complications	requiring intervention	0-30 days post ablation
Secondary	Heart block requiring pacemaker	Heart block requiring pacemaker	0-30 days post ablation
Secondary	Oesophageal dysmotility or gastroparesis	Oesophageal dysmotility or gastroparesis	0-30 days post ablation
Secondary	Phrenic nerve block	Phrenic nerve block	30 days, 12 and 24 months
Secondary	Symptomatic pulmonary vein stenosis	Symptomatic pulmonary vein stenosis	12 and 24 months
Secondary	Atrio-esophageal fistula	Atrio-esophageal fistula	12 and 24 months