Paroxysmal Atrial Fibrillation
Conditions
Keywords
Symptomatic Paroxysmal Atrial Fibrillation, pulmonary vein isolation, cryoballoon
Brief summary
Pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). Single shot devices are increasingly used for PVI. Currently, Medtronic Arctic Front cryoballoon is the most frequently used single shot technology and hence is the benchmark for upcoming technologies. A novel cryoballoon technology has recently been introduced (PolarX, Boston Scientific). However, whether PolarX provides effectiveness similar to the standard-of-practice Medtronic Arctic Front cryoballoon is yet to be investigated. Given that PolarX was developed considering the reported limitations and potential failures associated with the Medtronic Arctic Front cryoballoon, it might be even more effective and safe for use in AF ablation procedures. The aim of this trial is to compare the efficacy and safety of the PolarX Cryoballoon (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 single shot PVI and the PolarX is the novel technology, this trial has a non-inferiority design. The hypothesis with regards to the primary efficacy endpoint is that the PolarX Cryoballoon (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 PolarX Cryoballoon is non-inferior to the Arctic Front Cryoballoon. Rejection of the null hypothesis is needed to conclude non-inferiority.
Interventions
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 (Medtronic Reveal LINQ) will be implanted for the purpose of continuous arrhythmia monitoring.
DRUGPVI using the PolarX Cryoballoon (Boston Scientific)
Patients randomized to PolarX cryoballoon group will undergo PVI using the PolarX Cryoballoon (Boston Scientific). At the end of the procedure, an implantable cardiac monitor (Medtronic Reveal LINQ) will be implanted for the purpose of continuous arrhythmia monitoring.
Sponsors
Insel Gruppe AG, University Hospital Bern
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Paroxysmal atrial fibrillation documented on a 12 lead electrocardiogram (ECG) or Holter monitor (lasting ≥30 seconds) within the last 24 months. According to current guidelines, paroxysmal is defined as any atrial fibrillation (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 warfarin (International Normalized Ratio \[INR\] 2-3) or a novel oral anticoagulant (NOAC) for ≥4 weeks prior to the ablation; or a transesophageal echocardiogram (TEE) 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 (Appendix Informed Consent Form)
Exclusion criteria
* Previous LA ablation or LA surgery * AF due to reversible causes (e.g. hyperthyroidism, cardiothoracic surgery) * Intracardiac thrombus * Pre-existing pulmonary vein stenosis or pulmonary vein stent * Pre-existing hemidiaphragmatic paralysis * Contraindication to anticoagulation or radiocontrast materials * Cardiac valve prosthesis * Clinically significant (moderately-severe or severe) mitral regurgitation or stenosis * Myocardial infarction, percutaneous coronary intervention (PCI)/ percutaneous transluminal coronary angioplasty (PTCA), or coronary artery stenting during the 3-month period preceding the consent date * Cardiac surgery during the three-month interval preceding the consent date or scheduled cardiac surgery/transcatheter aortic valve implantation (TAVI) procedure * Significant congenital heart defect (including atrial septal defects or pulmonary vein abnormalities but not including patent foramen ovale) * New York Heart Association (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; estimated glomerular filtration rate \[eGFR\] \<30 μMol/L) * Uncontrolled hyperthyroidism * Cerebral ischemic event (stroke or TIA) during the six-month interval preceding the consent date * Ongoing systemic infections * History of cryoglobulinemia * Pregnancy\* * Life expectancy less than one (1) year per physician opinion * Currently participating in any other clinical trial of a drug, device or biological material during the duration of this study. * Unwilling or unable to comply fully with study procedures and follow-up. * To exclude pregnancy a blood test (human chorionic gonadotropin \[HCG\]) is used.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Recurrence of Any Atrial Tachyarrhythmia | days 91 to 365 post-ablation | Number of patients with 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complications | days 0 to 30 post-ablation | Composite endpoint composed of: * cardiac tamponade requiring drainage * persistent phrenic nerve palsy lasting \>24 hours * serious vascular complications requiring intervention * stroke/TIA * atrioesophageal fistula * death |
| Total Procedure Time | Day 1 | Total procedure time from femoral vein puncture to sheath removal |
| Total Left Atrial (LA) Indwelling Time | Day 1 | Total LA indwelling time, from transseptal puncture to removal of LA catheters |
| Total Cryoablation Time | Day 1 | procedural endpoint |
| Total Number of Cryoapplications Per Patient/Per Vein | Day 1 | procedural endpoint |
| Time to Effect | Day 1 | disappearance of PV-Signal; procedural endpoint |
| Nadir Temperatures | Day 1 | procedural endpoint |
| Total Fluoroscopy Time | Day 1 | procedural endpoint |
| Radiation Dose | Day 1 | procedural endpoint |
| Contrast Agent Usage | Day 1 | unit measure ml; procedural endpoint |
| Number of Patients With Veins With PV Signals Visible Before Cryoablation | Day 1 | procedural endpoint |
| Number of Participants With Phrenic Nerve Palsy | Day 1 | procedural endpoint |
| Number of Patients With Recurrence of Atrial Tachyarrhythmia | between days 1 and 90 after ablation | Follow up Endpoint |
| Overall AF Burden = % Time in AF | 91-365 days | Assessed by the ICM Core Lab post implantation |
| Number of Hospital Admissions or Emergency Room Visits Because of Documented Recurrence of Atrial Arrhythmias | Day 0 (after ablation) until day 365 post-ablation | based on telephone follow-up |
| Number of Electrical Cardioversion Because of Documented Recurrence of Atrial Arrhythmias | Day 0 (post-ablation) to day 365 after ablation | based on telephone follow-up |
| Number of Repeat Ablation Procedure Because of Documented Recurrence of Atrial Arrhythmias | Day 1 - 365 postablation | based on telephone follow-up |
| Evolution of Quality of Life (QoL) | Change in score from BL to 12 months | Evolution of Quality of Life (QoL) from BL to 12 months. Patients rated their health on a scale from 0 to 100, with 100 being the best possible score and 0 the worst possible score. A positive number in the outcome measure means that BL's health has improved at 12 months. A negative number in the outcome measure means that BL's health has declined at 12 months. |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORTobias Reichlin, MD
Inselspital, Bern University Hospital
Participant flow
Recruitment details
A total of 202 subjects were randomized at 2 sites in Switzerland between March 29, 2021 and June 14, 2022. The last 3-year follow-up visit occurred on July 24, 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.7 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 99 |
| other Total, other adverse events | 7 / 102 | 9 / 99 |
| serious Total, serious adverse events | 13 / 102 | 19 / 99 |
Outcome results
None listed