Comparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF (COMPARE-CRYO)

February 17, 2025 updated by: Insel Gruppe AG, University Hospital Bern

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

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 Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

201

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PVI using the 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 (Medtronic Reveal LINQ) will be implanted for the purpose of continuous arrhythmia monitoring.

Other Names:
  • Arctic Front Cryoballoon
Active Comparator: PVI using the PolarX Cryoballoon (Boston Scientific)
Pulmonary vein isolation using the PolarX Cryoballoon (Boston Scientific)
Drug: PVI 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.

Other Names:
  • PolarX Cryoballoon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first recurrence of any atrial tachyarrhythmia
Time Frame: days 91 to 365 post-ablation
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
Time Frame: 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
days 0 to 30 post-ablation
Total procedure time
Time Frame: Day 1
procedural endpoint
Day 1
Total LA indwelling time
Time Frame: Day 1
procedural endpoint
Day 1
Total cryoablation time
Time Frame: Day 1
procedural endpoint
Day 1
Total number of cryoapplications per patient/per vein
Time Frame: Day 1
procedural endpoint
Day 1
Time to effect
Time Frame: Day 1
disappearance of PV-Signal; procedural endpoint
Day 1
Nadir temperatures
Time Frame: Day 1
procedural endpoint
Day 1
Total fluoroscopy time
Time Frame: Day 1
procedural endpoint
Day 1
Radiation dose
Time Frame: Day 1
procedural endpoint
Day 1
Contrast agent usage
Time Frame: Day 1
unit measure ml; procedural endpoint
Day 1
Proportion of veins with PV signals visible before cryoablation
Time Frame: Day 1
procedural endpoint
Day 1
Rate of Phrenic nerve palsy
Time Frame: Day 1
procedural endpoint
Day 1
Changes in high sensitive Troponin (hsTroponin)
Time Frame: Day 1
one day 1 post-ablation ; procedural endpoint
Day 1
Time to first symptomatic recurrence of atrial tachyarrhythmia
Time Frame: between 91-365 days after ablation
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.
between 91-365 days after ablation
Time to first recurrence of atrial tachyarrhythmia
Time Frame: between days 1 and 90 after ablation
Follow up Endpoint.
between days 1 and 90 after ablation
Arrhythmia burden (daily AF burden [hours/day]; overall AF burden = % time in AF)
Time Frame: between: 0-90 days; 91-365 days , 365 days up to 3.5 years
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 burden calculated for 7-day intervals (daily AF burden [hours/day]; overall AF burden = % time in AF)
Time Frame: 3, 6 and 12 months follow up
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.
3, 6 and 12 months follow up
Comparison of the prevalence of the type of arrhythmia
Time Frame: 3, 12, 24 and 36 months follow up
Arrhythmia being AF or organized atrial arrhythmias (Atrial flutter or atrial tachycardias). Follow up Endpoint.
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
Time Frame: postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
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
Time Frame: postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
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
Time Frame: postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
based on telephone follow-up
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
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
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
during redo-procedure
Evolution of Quality of Life (QoL)
Time Frame: Months 3, 12, 24 and 36 post procedure
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
Months 3, 12, 24 and 36 post procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Collaborators

University Hospital, Basel, Switzerland

Investigators

  • Principal Investigator: Tobias Reichlin, MD, Inselspital, Bern University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2021

Primary Completion (Actual)

July 31, 2023

Study Completion (Estimated)

July 31, 2025

Study Registration Dates

First Submitted

December 10, 2020

First Submitted That Met QC Criteria

January 11, 2021

First Posted (Actual)

January 12, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 17, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-02076

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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