FIRE AND ICE: Comparative Study of Two Ablation Procedures in Patients With Atrial Fibrillation

A Controlled, Prospective, Non-Inferiority, Parallel-Group, Randomised, Interventional, Open, Blinded Outcome Assessment (PROBE-Design), Multi-centre Trial, Comparing Efficacy and Safety of Isolation of the PVs With a Cryoballoon Catheter vs a Radiofrequency Ablation With a ThermoCool Catheter in Patients With PAF

Comparing efficacy and safety of isolation of the pulmonary veins (PV) using a Cryoballoon catheter versus a radiofrequency ablation with a ThermoCool catheter in patients with paroxysmal atrial fibrillation.

The purpose of this randomized clinical trial is to compare the efficacy and safety of isolating the PVs with either the cryoballoon or a RF ablation technique with a ThermoCool catheter, a system which can be regarded as standard for ablation. In total 762 patients with paroxysmal atrial fibrillation has been randomized for either radiofrequency (RF) or cryoballoon. With both techniques, PV isolation will be performed. Primary end point of the trial is the time to first recurrence of atrial arrhythmias or prescription of anti-arrhythmic drugs after a blanking period of three months. Treatment success will be evaluated by using weekly electrocardiography (ECG) monitoring (transtelephonic transmission/Tele-ECG) and using Holter electrocardiograms.

Inclusion Criteria:

• Symptomatic PAF with at least two episodes and at least one episode documented (30 seconds episode length, documented by ECG within last 12 months).
• Documented treatment failure for effectiveness of at least one anti-arrhythmic drug(AAD Type I or III, including β-blocker and AAD intolerance).
• ≥ 18 and ≤ 75 years of age.
• Patients who are mentally and linguistically able to understand the aim of the trial and to show sufficient compliance in following the trial protocol.
• Patient is able to verbally acknowledge and understand the associated risks, benefits, and treatment alternatives to therapeutic options of this trial: cryoballoon ablation system or standard RF ablation technique. The patients, by providing informed consent, agree to these risks and benefits as stated in the patient informed consent document. All the details have been presented to him and he has signed the informed consent form for the trial.

Exclusion Criteria:

General exclusion criteria

• Any disease that limits life expectancy to less than one year.
• Participation in another clinical trial (of a drug, device or biologic), either within the past two months or ongoing.
• Pregnant women or women of childbearing potential not on adequate birth control: only women with a highly effective method of contraception [oral contraception or intrauterine device (IUD)] or sterile women can be randomized.
• Breastfeeding women.
• Substance misuse.
• Active systemic infection.
• Cryoglobulinaemia.
• Previous participation in this clinical trial.
• Employment by the sponsor or by the department of any of the investigators.
• Close relatives of any of the investigators.

Exclusion criteria related to a cardiac condition

• Patients with prosthetic valves.
• Any previous LA ablation or surgery.
• Any cardiac surgery or percutaneous coronary intervention (PCI) within three months prior to enrollment.
• Unstable angina pectoris.
• Myocardial infarction within three months prior to enrollment.
• Symptomatic carotid stenosis.
• Chronic obstructive pulmonary disease with detected pulmonary hypertension.
• Any condition contraindicating chronic anticoagulation.
• Stroke or transient ischemic attack within six months prior to enrollment.
• Any significant congenital heart defect corrected or not (including atrial septal defects or PV abnormalities) but not including patent foramen ovale.
• New York Heart Association (NYHA) class III or IV congestive heart failure.
• EF < 35 % (determined by echocardiography within 60 days of enrollment as documented in patient medical history).
• Anteroposterior LA diameter > 55 mm (by trans-thoracic echocardiography (TTE or TEE) within three months to prior enrollment).
• LA thrombus (TEE diagnostic performed on admission).
• Intracardiac thrombus.
• PV diameter > 26 mm in right sided PVs.
• Mitral prosthesis.
• Hypertrophic cardiomyopathy (see Appendix IX)
• 2° (Type II) or 3° atrioventricular block.
• Brugada syndrome or long QT syndrome.
• Arrhythmogenic right ventricular dysplasia.
• Sarcoidosis.
• PV stent.
• Myxoma.

Exclusion criteria based on laboratory abnormalities

• Thrombocytosis (platelet count > 600,000 / µl), thrombocytopenia (platelet count < 100,000 / µl).
• Any untreated or uncontrolled hyperthyroidism or hypothyroidism.
• Severe renal dysfunction (stage V, requiring or almost requiring dialysis, glomerular filtration rate (GFR) < 15 ml / min).