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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Symptomatic Paroxysmal Atrial Fibrillation (PAF)

Intervention / Treatment
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* Procedure: Electrical isolation of the pulmonary veins
* Procedure: Electrical isolation of pulmonary veins


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cryoballoon ablation<br> | Procedure: Electrical isolation of the pulmonary veins<br>* Device: ArcticFront® Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or ArcticFront® Advance Cardiac CryoAblation Catheter System with the FlexCath Steerable Sheath or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.<br>|
| Active Comparator: Radiofrequency ablation<br> | Procedure: Electrical isolation of pulmonary veins<br>* Device:NaviStar® ThermoCool® Irrigated Tip Ablation Catheter in combination with 3D mapping system CARTO or any future development generations of this product line, provided they are CE marked and the centre has the experience of at least 10 procedures before including a patient into the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Recurrence of Atrial Arrhythmias or Prescription of Anti-arrhythmic Drug or Re-ablation After a Blanking Period of Three Months After the Initial Ablation Procedure | Number of subjects reporting a primary efficacy endpoint | 33 months | 
| Number of Subjects With a Primary Safety Event. A Primary Safety Event Includes a Composite of Death (Including Cardiovascular Death), All-cause Stroke/Transient Ischemic Attack (TIA) and Serious Adverse Events of Special Interest. |  | 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Death |  | 33 months | 
| Arrhythmia-related Death |  | 33 months | 
| Total Procedure Duration |  | Through the initial ablation procedure | 
| Total Time of Fluoroscopy |  | Fluoroscopy meter time through the initial ablation procedure | 
| Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study. |  | 33 months | 
| Number of Cardiovascular Hospitalizations | The total number of cardiovascular hospitalizations reported over the duration of the study. | 33 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAF, two episodes within the last twelve months one episode documented, Documented treatment failure of at least one antiarrhythmic, drug AAD Type I or III including β-blocker and AAD intolerance