Clinical trial NCT05534581: SINGLE SHOT CHAMPION
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Paroxysmal Atrial Fibrillation
Keywords: Pulmonary vein isolation
Cryoballoon
Pulsed field ablation
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
First posted: 2022-09-09
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to first recurrence of any atrial tachyarrhythmia
timeFrame: Days 91 to 365 post-ablation
Secondary outcomes:
measure: Number of participants with complications
timeFrame: Days 0 to 30 post-ablation
measure: Total procedure time
timeFrame: Day 0
measure: Total left atrium indwelling time
timeFrame: Day 0
measure: Total fluoroscopy time
timeFrame: day 0
measure: Total radiation dose
timeFrame: Day 0
measure: Contrast agent usage
timeFrame: Day 0
measure: Increase in hsTroponin on day 1 post-ablation
timeFrame: Day 1
measure: Proportion of isolated veins
timeFrame: Day 0
measure: Proportion of isolated carinas
timeFrame: Day 0
measure: Lesion size
timeFrame: Day 0
measure: Time to first recurrence of atrial tachyarrhythmia between days 1 and 90 after ablation
timeFrame: Days 1 to 90 post-ablation
measure: Arrhythmia burden evaluated based on continuous ICM (overall AF burden = % time in AF)
timeFrame: Between: 0-90 days, 91-365 days, 365 days up to 3.5 years
measure: Arrhythmia being AF or organized atrial arrhythmias (atrial flutter or atrial tachycardias)
timeFrame: 3, 12, 24 and 36 months follow up
measure: Average heart rates
timeFrame: Months 1, 2 and 3 post-ablation
measure: Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias
timeFrame: Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
measure: Proportion of patients undergoing electrical cardioversion because of documented recurrence of atrial arrhythmias
timeFrame: Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
measure: Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias
timeFrame: Postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
measure: Reinitiation of antiarrhythmic drugs during follow-up
timeFrame: Months 3, 12, 24 and 36 post-ablation
measure: Number of reconnected veins evaluated during redo-procedures
timeFrame: During redo-procedure, expected to be on average 20-60 minutes
measure: Evolution of Quality of Life through months 3 and 12
timeFrame: Months 3 and 12 post-ablation
measure: Stroke including TIA after 3, 12, 24 and 36 months
timeFrame: Months 3, 12, 24 and 36 post-ablation
measure: Death cardiovascular or non-cardiovascular after 3, 12, 24 and 36 months
timeFrame: Months 3, 12, 24 and 36 post-ablation
measure: Sites (anatomical location) of vein reconnection assessed in study patients undergoing a Redo-Procedure at one of the study centres
timeFrame: During redo-procedure, expected to be on average 20-60 minutes
measure: Size (area calculate in cm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centres
timeFrame: During redo-procedure, expected to be on average 20-60 minutes
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital
Study officials:
affiliation: Inselspital, Bern University Hospital
name: Tobias Reichlin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, Dukkipati SR, Jais P. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019 Jul 23;74(3):315-326. doi: 10.1016/j.jacc.2019.04.021. Epub 2019 May 11.