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

Not Applicable

Completed

• Conditions: Symptomatic Paroxysmal Atrial Fibrillation (PAF)
• Interventions: Procedure: Electrical isolation of the pulmonary veins; Procedure: Electrical isolation of pulmonary veins

• Registration Number: NCT01490814
• Lead Sponsor: Medtronic Atrial Fibrillation Solutions

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-06
• Study First Submitted QC: 2011-12-09
• Study First Posted: 2011-12-13
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Results First Submitted: 2017-02-16
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-02
• Last Update Submitted: 2018-03-02
• Results First Posted: 2018-11-02
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 769

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cryoballoon ablation	Electrical isolation of the pulmonary veins	-
Radiofrequency ablation	Electrical isolation of pulmonary veins	-

Primary Outcome Measures

Name	Time	Method
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	33 months	Number of subjects reporting a primary efficacy endpoint
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

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

Trial Locations

Locations (19)

Semmelweis University of Medicine, Kardiovaskuläres Zentrum; 🇭🇺 Budapest, Hungary

Hospital Henri Mondor CHU, Service de Cardiologie; 🇫🇷 Créteil, France

Na Homolce Hospital, Cardiology; 🇨🇿 Prague, Czechia

CHU Lyon, Départment de Rythmologie, Hospital Cardiologique Pradel; 🇫🇷 Lyon, France

Centre Chirurgical Ambroise Paré; 🇫🇷 Neuilly Sur Seine, France

Klinik für Kardiologie II mit interventioneller Elektrophysiologie; 🇩🇪 Bad Neustadt/Saale, Germany

Herz-Zentrum Bad Krozingen; 🇩🇪 Bad Krozingen, Germany

La Clinique Pasteur, 45 Avenue de Lombez; 🇫🇷 Toulouse, France

Universitätsklinikum Greifswald Elektrophysiologie; 🇩🇪 Greifswald, Germany

Cardioangiologisches Centrum Bethanien - CCB; 🇩🇪 Frankfurt, Germany

Herz-Zentrum-Bodensee Konstanz; 🇩🇪 Konstanz, Germany

Asklepios Klinik St. Georg; 🇩🇪 Hamburg, Germany

Cardiac Arrhythmia Research Centre Department of Cardiovascular Medicine Centro Cardiologico Monzino University of Milan; 🇮🇹 Milan, Italy

Isala Klinieken loc. Weezenlanden Diagram Clinical Resarch; 🇳🇱 Zwolle, Netherlands

Hospital Universitario Virgen de la Victoria, Department of Cardiology, Campus Teatinos sn; 🇪🇸 Malaga, Spain

Arrhythmia Unit Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Clinico Universtitario, Cardiology Department Arrhythmia Unit; 🇪🇸 Valencia, Spain

Hospital Clinic, University of Barcelona; 🇪🇸 Barcelona, Spain

Universitätsspital Basel, Elektrophysiologie/ Kardiologie; 🇨🇭 Basel, Switzerland