Comparison of Cryoballoon vs. Pulsed Field Ablation in Patients With Symptomatic Paroxysmal Atrial Fibrillation

Single Shot Pulmonary Vein Isolation: Comparison of Cryoballoon vs. Pulsed Field Ablation in Patients With Symptomatic Paroxysmal Atrial Fibrillation - A Multi-Center Non-Inferiority Design Clinical Trial (The SINGLE SHOT CHAMPION Trial)

Pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). Currently, Medtronic Arctic Front Cryoballoon is the most frequently used single shot technology and hence is the benchmark for upcoming technologies. A novel method, pulse-field ablation (PFA) using the FARAPULSE catheter, has recently been introduced (FARAPULSE PFA, Boston Scientific). However, whether FARAPULSE PFA provides effectiveness similar to the standard-of-practice Medtronic Arctic Front Cryoballoon is yet to be investigated. Given that FARAPULSE PFA has shown in studies not to cause any of the severe complications reported in association with traditional PVI while being highly effective, it might be even safer and more effective for use in AF ablation procedures.

The aim of this trial is to compare the efficacy and safety of PVI using FARAPULSE PFA (Boston Scientific) and the Arctic Front Cryoballoon (Medtronic) in patients with symptomatic paroxysmal AF undergoing their first PVI.

This is an investigator-initiated, multicenter, randomized controlled, open-label trial with blinded endpoint adjudication. Given that the Medtronic Arctic Front Cryoballoon is the standard-of-practice for PVI and the FARAPULSE PFA is the novel technology, this trial has a non-inferiority design.

The null hypothesis with regards to the primary efficacy endpoint is that the FARAPULSE PFA (Boston Scientific) shows lower efficacy compared to the Arctic Front Cryoballoon (Medtronic) and that therefore more episodes of first recurrence of any atrial arrhythmia between days 91 and 365 will be observed in patients with symptomatic paroxysmal AF undergoing their first PVI. Hence, the alternative hypothesis postulates that the FARAPULSE PFA is non-inferior to the Arctic Front Cryoballoon. Rejection of the null hypothesis is needed to conclude non-inferiority.

Study Overview

• Status: Active, not recruiting
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Device: PVI using the Arctic Front Cryoballoon (Medtronic); Device: PVI using FARAPULSE Pulsed Field Ablation (Boston Scientific)

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
  • Bern, Switzerland, 3010
    • Inselspital, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Paroxysmal atrial fibrillation documented on a 12 lead ECG or Holter monitor (lasting ≥30 seconds) within the last 24 months. According to current guidelines, paroxysmal is defined as any AF that converts to sinus rhythm within 7 days either spontaneously or by pharmacological or electrical cardioversion
• Candidate for ablation based on current AF guidelines
• Continuous anticoagulation with Vitamin-K-Antagonists or a novel oral anticoagulant for ≥4 weeks prior to the ablation; or a transesophageal echocardiography and/or computer tomography that excludes left atrial (LA) thrombus ≤48 hours before ablation
• Age of 18 years or older on the date of consent
• Informed Consent as documented by signature

Exclusion Criteria:

• Previous left atrial (LA) ablation or LA surgery
• AF due to reversible causes (e.g. hyperthyroidism, cardiothoracic surgery)
• Intracardiac thrombus
• Pre-existing pulmonary vein stenosis or PV stent
• Pre-existing hemidiaphragmatic paralysis
• Contraindication to anticoagulation or radiocontrast materials
• Prior mitral valve surgery
• Severe mitral regurgitation or moderate/severe mitral stenosis
• Myocardial infarction during the 3-month period preceding the consent date
• Ongoing triple therapy
• Cardiac surgery during the three-month interval preceding the consent date or scheduled cardiac surgery/TAVI procedure
• Significant congenital heart defect (including atrial septal defects or PV abnormalities but not including PFO)
• NYHA class III or IV congestive heart failure
• Left ventricular ejection fraction (LVEF) <35%
• Hypertrophic cardiomyopathy (wall thickness >1.5 cm)
• Significant chronic kidney disease (CKD; eGFR <30 ml/min)
• Uncontrolled hyperthyroidism
• Cerebral ischemic event (stroke or TIA) during the six-month interval preceding the consent date
• Ongoing systemic infections
• History of cryoglobulinemia
• Cardiac amyloidosis
• Pregnancy
• Life expectancy less than one (1) year per physician opinion
• Currently participating in any other clinical trial, which may confound the results of this trial.
• Unwilling or unable to comply fully with study procedures and follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arctic Front Cryoballoon (Medtronic); Pulmonary vein isolation using the Arctic Front Cryoballoon (Medtronic)	Device: PVI using the Arctic Front Cryoballoon (Medtronic); Patients randomized to the Arctic Front cryoballoon group will undergo PVI using the Arctic Front Cryoballoon (Medtronic). At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring.
Active Comparator: Pulsed Field Ablation (FARAPULSE); Pulmonary vein isolation using the FARAPULSE PFA system (Boston Scientific)	Device: PVI using FARAPULSE Pulsed Field Ablation (Boston Scientific); Patients randomized to the Pulsed Field Ablation group will undergo PVI using the FARAPULSE PFA system (Boston Scientific). At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first recurrence of any atrial tachyarrhythmia	Time to first recurrence of any atrial tachyarrhythmia (atrial fibrillation [AF], atrial flutter [AFL] or atrial tachycardia [AT]) between days 91 and 365 post ablation as detected on continuous implantable cardiac monitor (ICM). AF, AFL or AT will qualify as a recurrence after ablation if it lasts 120 s or longer on ICM (the minimum programmable episode interval).	Days 91 to 365 post-ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with complications	Composite safety endpoint composed of: cardiac tamponade requiring drainage; persistent phrenic nerve palsy lasting >24 hours; serious vascular complications requiring intervention; stroke/TIA; atrioesophageal fistula; death	Days 0 to 30 post-ablation
Total procedure time	Procedural endpoint	Day 0
Total left atrium indwelling time	Procedural endpoint	Day 0
Total fluoroscopy time	Procedural endpoint	day 0
Total radiation dose	Procedural endpoint	Day 0
Contrast agent usage	Procedural endpoint	Day 0
Increase in hsTroponin on day 1 post-ablation	Procedural endpoint	Day 1
Proportion of isolated veins	Assessed by post-ablation 3D electro-anatomical mapping in the first 25 patients in each study group	Day 0
Proportion of isolated carinas	Assessed by post-ablation 3D electro-anatomical mapping in the first 25 patients in each study group	Day 0
Lesion size	Assessed by post-ablation 3D electro-anatomical mapping in the first 25 patients in each study group	Day 0
Time to first recurrence of atrial tachyarrhythmia between days 1 and 90 after ablation	Time to first recurrence of any atrial tachyarrhythmia (atrial fibrillation [AF], atrial flutter [AFL] or atrial tachycardia [AT]) between days 1 and 90 post ablation as detected on continuous implantable cardiac monitor (ICM). AF, AFL or AT will qualify as a recurrence after ablation if it lasts 120 s or longer on ICM (the minimum programmable episode interval).	Days 1 to 90 post-ablation
Arrhythmia burden evaluated based on continuous ICM (overall AF burden = % time in AF)	Assessed by the ICM Core Lab post implantation: between 0-90 days; 91-365 days, 365 days to explantation/end of life of the ICM	Between: 0-90 days, 91-365 days, 365 days up to 3.5 years
Arrhythmia being AF or organized atrial arrhythmias (atrial flutter or atrial tachycardias)	Comparison of the prevalence of the type of arrhythmia recurrences during follow-up being AF or organized atrial arrhythmias (AFL or AT)	3, 12, 24 and 36 months follow up
Average heart rates	Average heart rates in ICM documentation in months 1, 2 and 3 after ablation	Months 1, 2 and 3 post-ablation
Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias	Based on telephone follow-up	Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Proportion of patients undergoing electrical cardioversion because of documented recurrence of atrial arrhythmias	Based on telephone follow-up	Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias	Based on telephone follow-up	Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Reinitiation of antiarrhythmic drugs during follow-up	Reinitiation of antiarrhythmic drugs during follow-up based on telephone follow-up	Months 3, 12, 24 and 36 post-ablation
Number of reconnected veins evaluated during redo-procedures		During redo-procedure, expected to be on average 20-60 minutes
Evolution of Quality of Life through months 3 and 12	QoL questionnaires (EQ-5D) will be sent to the patients by mail after 3 and 12 months to compare the evolution of QoL after the ablation	Months 3 and 12 post-ablation
Stroke including TIA after 3, 12, 24 and 36 months		Months 3, 12, 24 and 36 post-ablation
Death cardiovascular or non-cardiovascular after 3, 12, 24 and 36 months		Months 3, 12, 24 and 36 post-ablation
Sites (anatomical location) of vein reconnection assessed in study patients undergoing a Redo-Procedure at one of the study centres		During redo-procedure, expected to be on average 20-60 minutes
Size (area calculate in cm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centres		During redo-procedure, expected to be on average 20-60 minutes

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: University of Bern
• Investigators: Principal Investigator: Tobias Reichlin, MD, Inselspital, Bern University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary vein isolation; Cryoballoon; Pulsed field ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2022-D0024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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