Clinical trial NCT04704986: Comparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF
Official title: Comparison of the PolarX and the Arctic Front Cryoballoon for Pulmonary Vein Isolation in Patients With Symptomatic Paroxysmal Atrial Fibrillation - A Multi-Center Non-Inferiority Design Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Paroxysmal Atrial Fibrillation
Keywords: Symptomatic Paroxysmal Atrial Fibrillation
pulmonary vein isolation
cryoballoon
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University Hospital, Basel, Switzerland
First posted: 2021-01-12
Enrollment: 201
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). 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.


Eligibility criteria: 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.

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 1
measure: Total LA indwelling time
timeFrame: Day 1
measure: Total cryoablation time
timeFrame: Day 1
measure: Total number of cryoapplications per patient/per vein
timeFrame: Day 1
measure: Time to effect
timeFrame: Day 1
measure: Nadir temperatures
timeFrame: Day 1
measure: Total fluoroscopy time
timeFrame: Day 1
measure: Radiation dose
timeFrame: Day 1
measure: Contrast agent usage
timeFrame: Day 1
measure: Proportion of veins with PV signals visible before cryoablation
timeFrame: Day 1
measure: Rate of Phrenic nerve palsy
timeFrame: Day 1
measure: Changes in high sensitive Troponin (hsTroponin)
timeFrame: Day 1
measure: Time to first symptomatic recurrence of atrial tachyarrhythmia
timeFrame: between 91-365 days after ablation
measure: Time to first recurrence of atrial tachyarrhythmia
timeFrame: between days 1 and 90 after ablation
measure: Arrhythmia burden (daily AF burden [hours/day]; overall AF burden = % time in AF)
timeFrame: between: 0-90 days; 91-365 days , 365 days up to 3.5 years
measure: Arrhythmia burden calculated for 7-day intervals (daily AF burden [hours/day]; overall AF burden = % time in AF)
timeFrame: 3, 6 and 12 months follow up
measure: Comparison of the prevalence of the type of arrhythmia
timeFrame: 3, 12, 24 and 36 months follow up
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: Number of reconnected veins assessed in study patients undergoing a Redo-Procedure at one of the study centres
timeFrame: during redo-procedure
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
measure: Size (area calculate in mm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centres
timeFrame: during redo-procedure
measure: Evolution of Quality of Life (QoL)
timeFrame: Months 3, 12, 24 and 36 post procedure
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
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