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

Paroxysmal Atrial Fibrillation Clinical Trial

— COMPARE-CRYO  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04704986
• Other study ID #: 2020-02076
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 29, 2021
• Est. completion date: July 31, 2025

Study information

• Verified date: February 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 201
• Est. completion date: July 31, 2025
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Paroxysmal Atrial Fibrillation

Intervention

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.

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.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel
Switzerland	Inselspital, Bern University Hospital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

References & Publications (26)

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	days 91 to 365 post-ablation
Secondary	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	days 0 to 30 post-ablation
Secondary	Total procedure time	procedural endpoint	Day 1
Secondary	Total LA indwelling time	procedural endpoint	Day 1
Secondary	Total cryoablation time	procedural endpoint	Day 1
Secondary	Total number of cryoapplications per patient/per vein	procedural endpoint	Day 1
Secondary	Time to effect	disappearance of PV-Signal; procedural endpoint	Day 1
Secondary	Nadir temperatures	procedural endpoint	Day 1
Secondary	Total fluoroscopy time	procedural endpoint	Day 1
Secondary	Radiation dose	procedural endpoint	Day 1
Secondary	Contrast agent usage	unit measure ml; procedural endpoint	Day 1
Secondary	Proportion of veins with PV signals visible before cryoablation	procedural endpoint	Day 1
Secondary	Rate of Phrenic nerve palsy	procedural endpoint	Day 1
Secondary	Changes in high sensitive Troponin (hsTroponin)	one day 1 post-ablation ; procedural endpoint	Day 1
Secondary	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.	between 91-365 days after ablation
Secondary	Time to first recurrence of atrial tachyarrhythmia	Follow up Endpoint.	between days 1 and 90 after ablation
Secondary	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	between: 0-90 days; 91-365 days , 365 days up to 3.5 years
Secondary	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.	3, 6 and 12 months follow up
Secondary	Comparison of the prevalence of the type of arrhythmia	Arrhythmia being AF or organized atrial arrhythmias (Atrial flutter or atrial tachycardias). Follow up Endpoint.	3, 12, 24 and 36 months follow up
Secondary	Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias	based on telephone follow-up	postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Secondary	Proportion of patients undergoing electrical cardioversion because of documented recurrence of atrial arrhythmias	based on telephone follow-up	postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Secondary	Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias	based on telephone follow-up	postablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)
Secondary	Number of reconnected veins assessed in study patients undergoing a Redo-Procedure at one of the study centres		during redo-procedure
Secondary	Sites (anatomical location) of vein reconnection assessed in study patients undergoing a Redo-Procedure at one of the study centres		during redo-procedure
Secondary	Size (area calculate in mm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centres		during redo-procedure
Secondary	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	Months 3, 12, 24 and 36 post procedure