Comparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF

Phase 4Active Not RecruitingNCT04704986

Insel Gruppe AG, University Hospital Bern201 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

PVI using the Arctic Front Cryoballoon (Medtronic)DEVICE

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.

PVI using the PolarX Cryoballoon (Boston Scientific)DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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).

Time frame: days 91 to 365 post-ablation

Secondary Outcomes

Number of participants with complications

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

Time frame: days 0 to 30 post-ablation

Total procedure time

procedural endpoint

Time frame: Day 1

Total LA indwelling time

procedural endpoint

Time frame: Day 1

Total cryoablation time

procedural endpoint

Time frame: Day 1

Total number of cryoapplications per patient/per vein

procedural endpoint

Time frame: Day 1

Time to effect

disappearance of PV-Signal; procedural endpoint

Time frame: Day 1

Nadir temperatures

procedural endpoint

Time frame: Day 1

Total fluoroscopy time

procedural endpoint

Time frame: Day 1

Radiation dose

procedural endpoint

Time frame: Day 1

Contrast agent usage

unit measure ml; procedural endpoint

Time frame: Day 1

Proportion of veins with PV signals visible before cryoablation

procedural endpoint

Time frame: Day 1

Rate of Phrenic nerve palsy

procedural endpoint

Time frame: Day 1

Changes in high sensitive Troponin (hsTroponin)

one day 1 post-ablation ; procedural endpoint

Time frame: Day 1

Time to first symptomatic recurrence of atrial tachyarrhythmia

Assessed by the ICM Core Lab. "Symptomatic" is defined as acute onset awareness of palpitations, breathlessness, dizziness, fatigue or chest pain associated with patient activation of the loop recorder. Follow up Endpoint.

Time frame: between 91-365 days after ablation

Time to first recurrence of atrial tachyarrhythmia

Follow up Endpoint.

Time frame: between days 1 and 90 after ablation

Arrhythmia burden (daily AF burden [hours/day]; 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

Time frame: between: 0-90 days; 91-365 days , 365 days up to 3.5 years

Arrhythmia burden calculated for 7-day intervals (daily AF burden [hours/day]; overall AF burden = % time in AF)

Comparison of full-duration ICM derived endpoints with standard clinical practice derived endpoints. Standard clinical practice being defined as 7d-Holter Periods after 3, 6 and 12 months (modelled with random 7day ICM periods after 3, 6 and 12 months). Follow up Endpoint.

Time frame: 3, 6 and 12 months follow up

Comparison of the prevalence of the type of arrhythmia

Arrhythmia being AF or organized atrial arrhythmias (Atrial flutter or atrial tachycardias). Follow up Endpoint.

Time frame: 3, 12, 24 and 36 months follow up

Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias

based on telephone follow-up

Time frame: 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

Time frame: 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

Time frame: postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)

Number of reconnected veins assessed in study patients undergoing a Redo-Procedure at one of the study centres

Time frame: during redo-procedure

Sites (anatomical location) of vein reconnection assessed in study patients undergoing a Redo-Procedure at one of the study centres

Time frame: during redo-procedure

Size (area calculate in mm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centres

Time frame: during redo-procedure

Evolution of Quality of Life (QoL)

QoL questionnaires (EQ-5D) will be sent to the patients by mail after 3, 12, 24 and 36 months to compare the evolution of QoL after the ablation

Time frame: Months 3, 12, 24 and 36 post procedure

Comparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes