First-line Cryoablation for Early Treatment of Persistent Atrial Fibrillation - a Randomized Study Comparing Early Trigger Isolation Using the Cryoballoon Versus Antiarrhythmic Medication

CryoStopPersAF

The goal of this multicentre, prospective, randomized, open, blinded for evaluation of end point (PROBE) controlled parallel-group superiority trial, is to compare the efficacy of antiarrhythmic drug (AAD) therapy and cryoballoon pulmonary vein isolation (PVI) regarding freedom from atrial fibrillation (%) assessed by an implantable cardiac monitor (ICM), ECG tracing or Holter at 12 months in patients with persistent AF. The main question\[s\] it aims to answer are: * Will first-line cryoballoon ablation for PVI compared to AAD, result in 25 % higher freedom from atrial tachyarrhythmias lasting \> 6 minutes at 12 months (primary outcome) excluding three months initial blanking period, in patients with symptomatic and recurrent persistent AF? * Will first-line cryoablation for PVI, compared to AAD result in a superior improvement in health related Quality of Life (HRQoL), AF/AT burden, AF/AT progression and reversion, more reverse atrial remodeling, cognitive function, healthcare utilization with associated costs, better safety, at 12-24-36 months as compared with drug use? Participants will be randomized 1:1 to first-line PVI using the cryoballoon or to first-line antiarrhythmic drug therapy and during 3 years follow-up undergo regular; * Continuous ECG monitoring for assessment of first AF recurrence and AF burden using an implantable cardiac monitor, * Regular echocardiographic exams for reverse atrial remodelling assessment, * HRQoL questionnaires * Assessment of cognitive function * Atrial fibrillation evaluation regarding structured characterisation and AF progression/regression * Assessment of Health care use and costs * Safety

2023-08-21

2027-12-01

2028-12-01

Not yet recruiting

Early phase I

220

Inclusion Criteria: * Non-longstanding persistent symptomatic AF with at least 2 episodes within last 24 months, the latest episode within the previous 6 months and one documented on a 12 lead ECG or Holter monitor, that is classified as either 1. Classical persistent AF (continuously sustained beyond 7 days and \<12 months in duration) as defined by ESC guidelines14 OR 2. Persistent AF which has progressed from paroxysmal AF (patients who have been cardioverted within 7 days of onset provided a history of spontaneous conversion to sinus rhythm is lacking during the past 24 months). * Candidate for rhythm control therapy; AF ablation or AAD based on symptomatic AF. Exclusion Criteria: 1. Regular daily use of AAD class I or III at adequate therapeutic dosages (pill-in-the-pocket permitted, beta-blockers permitted). 2. Previous AF ablation or surgery. 3. Severe heart failure (NYHA III-IV). 4. Reduced left ventricular ejection fraction (LVEF ≤40 % during sinus rhythm). 5. Hypertrophic cardiomyopathy (septal or posterior wall thickness \>1.5 cm) 6. Severely enlarged LA with left atrial volume indexed to body surface area (LAVI, ml/m2) \> 48. 7. Significant valvular disease requiring treatment or valve prothesis. 8. Severe Chronic Obstructive Pulmonary Disease (COPD) stage III or chronic kidney disease (eGFR\< 30 umol/l)). 9. Planned cardiac intervention within the next 12 months or cardiac surgery last 6 months. 10. Myocardial infarction, revascularisation previous 6 months. 11. Stroke or Transient Ischemic Attack (TIA) within previous 6 months. 12. Tachycardiomyopathy. 13. Dependent on VVI (ventricular single chamber inhibited) pacing. 14. Conventional contraindications for AF ablation including AF due to reversible causes and contraindications for both class IC and class III antiarrhythmic drugs. 15. Expected survival less than 3 years, alcohol or drug abuse. 16. Participation in another trial or absence of consent.

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2023-07-11