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

Phase 4
Active, not recruiting
Conditions
Paroxysmal Atrial Fibrillation
Interventions
Drug: PVI using the PolarX Cryoballoon (Boston Scientific)
Device: PVI using the Arctic Front Cryoballoon (Medtronic)
Registration Number
NCT04704986
Lead Sponsor
Insel Gruppe AG, University Hospital Bern
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
201
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PVI using the PolarX Cryoballoon (Boston Scientific)PVI using the PolarX Cryoballoon (Boston Scientific)Pulmonary vein isolation using the PolarX Cryoballoon (Boston Scientific)
PVI using the Arctic Front Cryoballoon (Medtronic)PVI using the Arctic Front Cryoballoon (Medtronic)Pulmonary vein isolation using the Arctic Front Cryoballoon (Medtronic)
Primary Outcome Measures
NameTimeMethod
Time to first recurrence of any atrial tachyarrhythmiadays 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).

Secondary Outcome Measures
NameTimeMethod
Total LA indwelling timeDay 1

procedural endpoint

Number of participants with complicationsdays 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

Total procedure timeDay 1

procedural endpoint

Total cryoablation timeDay 1

procedural endpoint

Total number of cryoapplications per patient/per veinDay 1

procedural endpoint

Time to effectDay 1

disappearance of PV-Signal; procedural endpoint

Nadir temperaturesDay 1

procedural endpoint

Total fluoroscopy timeDay 1

procedural endpoint

Radiation doseDay 1

procedural endpoint

Proportion of veins with PV signals visible before cryoablationDay 1

procedural endpoint

Contrast agent usageDay 1

unit measure ml; procedural endpoint

Changes in high sensitive Troponin (hsTroponin)Day 1

one day 1 post-ablation ; procedural endpoint

Time to first symptomatic recurrence of atrial tachyarrhythmiabetween 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.

Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmiaspostablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)

based on telephone follow-up

Sites (anatomical location) of vein reconnection assessed in study patients undergoing a Redo-Procedure at one of the study centresduring redo-procedure
Rate of Phrenic nerve palsyDay 1

procedural endpoint

Time to first recurrence of atrial tachyarrhythmiabetween days 1 and 90 after ablation

Follow up Endpoint.

Comparison of the prevalence of the type of arrhythmia3, 12, 24 and 36 months follow up

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

Proportion of patients undergoing electrical cardioversion because of documented recurrence of atrial arrhythmiaspostablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)

based on telephone follow-up

Arrhythmia burden (daily AF burden [hours/day]; overall AF burden = % time in AF)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

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

Number of reconnected veins assessed in study patients undergoing a Redo-Procedure at one of the study centresduring redo-procedure
Size (area calculate in mm2) of antral scar area assessed in study patients undergoing a Redo-Procedure at one of the study centresduring redo-procedure
Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmiaspostablation 3 months (+/- 2 weeks), 12 months (+/- 2 months), 24 months (+/- 2 months) and 36 months (+/- 2 months)

based on telephone follow-up

Evolution of Quality of Life (QoL)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

Trial Locations

Locations (2)

University Hospital Basel

🇨🇭

Basel, Switzerland

Inselspital, Bern University Hospital

🇨🇭

Bern, Switzerland

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