Methods:
Design: FROZEN-AF is a prospective, non-randomized, multi-center, investigation conducted to establish the safety and effectiveness of the POLARx cryoablation system in subjects with symptomatic, drug refractory, recurrent, paroxysmal atrial fibrillation. The trial was registered at clinical trials.gov (NCT04133168). All patients provide written informed consent to participate in the trial and all centers obtained approval by their local IRB.
Subjects: Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of 1 or more antiarrhythmic drugs. To allow orientation to the new investigational system and minimize potential learning curve bias each ablating physician was required to treat one “roll-in” patient. Sixty-three total roll-in patients were treated, their data is not reported here. Briefly, patients were indicated for PVI to treat recurrent symptomatic AF and had failed at least one Class I or III antiarrhythmic drug (AAD) and had not been on amiodarone for at least 90 days. Patients were excluded if they had contraindications for AF ablation (or anticoagulants), continuous AF (longer than 7 days), a history of prior left atrial ablation for AF/AFL/AT, structural heart disease of implanted cardiac devices. For full inclusion and exclusion criteria, see supplement.
All subjects fitting the enrollment criteria, signing the consent and undergoing the index procedure with the study devices were followed for up to 12 months after the index procedure. FROZEN-AF was conducted as a post market study in those regions where the device was already approved, including Europe.
Site description : Investigators and sites were selected based on prior experience with cryoablation, ensuring that sites had adequate access to subject population, staff, and documentation practices. In total, 44 sites participated in the study, 30 in the United States, 6 in Europe, 4 in Canada, and 4 in Asia/ Pacific.
Patient Flow: In total, 404 subjects were enrolled across 44 centers (30 in the US, 6 in Europe, 4 in Canada, and 4 in Asia/ Pacific). Of these 385 subjects received treatment with the investigational device, 60 treatment subjects were classified as roll-In subjects and 325 as non-roll-in subjects. Fifteen treatment patients and 4 “roll-in” patients withdrew consent from the study, which was in line with the protocol assumed 10% attrition. Additionally, as part of an extension arm, 54 patients were enrolled to examine the safety and effectiveness of the novel variable size cryoballoon POLARx FITTm (Boston Scientific, MN, USA). Of these, there was 1 consent ineligible, 3 intent to treat, and 50 treatment patients.