Paroxysmal Atrial FibrillationPhase 4COMPARE-CRYONCT04704986
Comparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF
A Phase 4 study testing PVI using the Arctic Front Cryoballoon (Medtronic) and PVI using the PolarX Cryoballoon (Boston Scientific) in people with Paroxysmal Atrial Fibrillation, run by Insel Gruppe AG, University Hospital Bern at 2 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Atrial Fibrillation
- What is being tested?
- PVI using the Arctic Front Cryoballoon (Medtronic) and PVI using the PolarX Cryoballoon (Boston Scientific)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 29 Mar 2021to 24 Jul 2025
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 24Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
University Hospital Basel
Basel, 4031
Inselspital, Bern University Hospital
Bern, 3010
About this study
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
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.
Read more
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.
- Conditions
- Paroxysmal Atrial Fibrillation
- Being tested
- PVI using the Arctic Front Cryoballoon (Medtronic), PVI using the PolarX Cryoballoon (Boston Scientific)
- Keywords
- Symptomatic Paroxysmal Atrial Fibrillation, pulmonary vein isolation, cryoballoon
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PVI using the Arctic Front Cryoballoon (Medtronic)Device
Also called Arctic Front Cryoballoon
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
Also called PolarX Cryoballoon
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.
| Study group | Role | What they receive |
|---|---|---|
| PVI using the Arctic Front Cryoballoon (Medtronic) | Active comparator | Pulmonary vein isolation using the Arctic Front Cryoballoon (Medtronic) Receives: Device: PVI using the Arctic Front Cryoballoon (Medtronic) |
| PVI using the PolarX Cryoballoon (Boston Scientific) | Active comparator | Pulmonary vein isolation using the PolarX Cryoballoon (Boston Scientific) Receives: Drug: PVI using the PolarX Cryoballoon (Boston Scientific) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Recurrence of Any Atrial Tachyarrhythmia
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).
Measured: days 91 to 365 post-ablation
Secondary outcomes (18)
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
Measured: days 0 to 30 post-ablation
Total Procedure Time
Total procedure time from femoral vein puncture to sheath removal
Measured: Day 1
Total Left Atrial (LA) Indwelling Time
Total LA indwelling time, from transseptal puncture to removal of LA catheters
Measured: Day 1
Total Cryoablation Time
procedural endpoint
Measured: Day 1
Total Number of Cryoapplications Per Patient/Per Vein
procedural endpoint
Measured: Day 1
Time to Effect
disappearance of PV-Signal; procedural endpoint
Measured: Day 1
Nadir Temperatures
procedural endpoint
Measured: Day 1
Total Fluoroscopy Time
procedural endpoint
Measured: Day 1
Radiation Dose
procedural endpoint
Measured: Day 1
Contrast Agent Usage
unit measure ml; procedural endpoint
Measured: Day 1
Number of Patients With Veins With PV Signals Visible Before Cryoablation
procedural endpoint
Measured: Day 1
Number of Participants With Phrenic Nerve Palsy
procedural endpoint
Measured: Day 1
Number of Patients With Recurrence of Atrial Tachyarrhythmia
Follow up Endpoint
Measured: between days 1 and 90 after ablation
Overall AF Burden = % Time in AF
Assessed by the ICM Core Lab post implantation
Measured: 91-365 days
Number of Hospital Admissions or Emergency Room Visits Because of Documented Recurrence of Atrial Arrhythmias
based on telephone follow-up
Measured: Day 0 (after ablation) until day 365 post-ablation
Number of Electrical Cardioversion Because of Documented Recurrence of Atrial Arrhythmias
based on telephone follow-up
Measured: Day 0 (post-ablation) to day 365 after ablation
Number of Repeat Ablation Procedure Because of Documented Recurrence of Atrial Arrhythmias
based on telephone follow-up
Measured: Day 1 - 365 postablation
Evolution of Quality of Life (QoL)
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.
Measured: Change in score from BL to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study start29 Mar 2021
- Primary completion31 Jul 2023
- Study completion24 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Basel, Switzerland
- Responsible party
- Sponsor
- Investigators
- Tobias Reichlin, MD, Principal investigator, Inselspital, Bern University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04704986
- Sponsor's protocol ID
- 2020-02076
- Acronym
- COMPARE-CRYO
- Status last verified
- Apr 2026
- First submitted
- 10 Dec 2020
- Last updated
- 24 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Chung MK, Refaat M, Shen WK, Kutyifa V, Cha YM, Di Biase L, Baranchuk A, Lampert R, Natale A, Fisher J, Lakkireddy DR; ACC Electrophysiology Section Leadership Council. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. 2020 Apr 14;75(14):1689-1713. doi: 10.1016/j.jacc.2020.02.025.
PubMed 32273035Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22(8):983-8. doi: 10.1161/01.str.22.8.983.
PubMed 1866765Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003 Jun 17;107(23):2920-5. doi: 10.1161/01.CIR.0000072767.89944.6E. Epub 2003 May 27.
PubMed 12771006Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998 Sep 8;98(10):946-52. doi: 10.1161/01.cir.98.10.946.
PubMed 9737513Chen LY, Sotoodehnia N, Buzkova P, Lopez FL, Yee LM, Heckbert SR, Prineas R, Soliman EZ, Adabag S, Konety S, Folsom AR, Siscovick D, Alonso A. Atrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study. JAMA Intern Med. 2013 Jan 14;173(1):29-35. doi: 10.1001/2013.jamainternmed.744.
PubMed 23404043Soliman EZ, Safford MM, Muntner P, Khodneva Y, Dawood FZ, Zakai NA, Thacker EL, Judd S, Howard VJ, Howard G, Herrington DM, Cushman M. Atrial fibrillation and the risk of myocardial infarction. JAMA Intern Med. 2014 Jan;174(1):107-14. doi: 10.1001/jamainternmed.2013.11912.
PubMed 24190540Soliman EZ, Lopez F, O'Neal WT, Chen LY, Bengtson L, Zhang ZM, Loehr L, Cushman M, Alonso A. Atrial Fibrillation and Risk of ST-Segment-Elevation Versus Non-ST-Segment-Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2015 May 26;131(21):1843-50. doi: 10.1161/CIRCULATIONAHA.114.014145. Epub 2015 Apr 27.
PubMed 25918127Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available.
PubMed 27567408Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, Lehmann JW, Ruskin JN; STOP AF Cryoablation Investigators. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013 Apr 23;61(16):1713-23. doi: 10.1016/j.jacc.2012.11.064. Epub 2013 Mar 21.
PubMed 23500312Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):333-40. doi: 10.1001/jama.2009.2029.
PubMed 20103757Jais P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M, Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clementy J, Haissaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation. 2008 Dec 9;118(24):2498-505. doi: 10.1161/CIRCULATIONAHA.108.772582. Epub 2008 Nov 24.
PubMed 19029470Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL; CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274. doi: 10.1001/jama.2019.0693.
PubMed 30874766Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.
PubMed 27042964Jourda F, Providencia R, Marijon E, Bouzeman A, Hireche H, Khoueiry Z, Cardin C, Combes N, Combes S, Boveda S, Albenque JP. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Europace. 2015 Feb;17(2):225-31. doi: 10.1093/europace/euu215. Epub 2014 Sep 3.
PubMed 25186456Squara F, Zhao A, Marijon E, Latcu DG, Providencia R, Di Giovanni G, Jauvert G, Jourda F, Chierchia GB, De Asmundis C, Ciconte G, Alonso C, Grimard C, Boveda S, Cauchemez B, Saoudi N, Brugada P, Albenque JP, Thomas O. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. 2015 May;17(5):718-24. doi: 10.1093/europace/euv060. Epub 2015 Apr 2.
PubMed 25840289