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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01490814
Recruitment Status : Completed
First Posted : December 13, 2011
Last Update Posted : May 10, 2016
Information provided by (Responsible Party):
Medtronic International Trading Sarl

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.

Condition or disease Intervention/treatment Phase
Symptomatic Paroxysmal Atrial Fibrillation (PAF) Procedure: Electrical isolation of the pulmonary veins Procedure: Electrical isolation of pulmonary veins Not Applicable

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 769 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2011
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Cryoballoon ablation Procedure: Electrical isolation of the pulmonary veins
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.
Active Comparator: Radiofrequency ablation Procedure: Electrical isolation of pulmonary veins
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.

Primary Outcome Measures :
  1. Time to first documented recurrence of atrial arrhythmias (a blanking period of three months will be maintained after the initial procedure). [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. time to the first occurrence of each of the components of the primary outcome [ Time Frame: 18 months ]
    The secondary outcome parameters are defined as all-cause death; Arrhythmia-related death; total procedural duration; total time of fluoroscopy; time to the first occurrence of each of the components of the primary outcome; time to recurrent atrial fibrillation (AF); time to first cardiovascular hospitalization; number of cardiovascular hospitalizations (over-night stays); quality of life changes at 12 months compared to baseline; time to first symptomatic AF recurrence;

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01490814

Czech Republic
Na Homolce Hospital, Cardiology
Prague, Czech Republic, 515030
Hospital Henri Mondor CHU, Service de Cardiologie
Créteil, France, 94010
CHU Lyon, Départment de Rythmologie, Hospital Cardiologique Pradel
Lyon, France, 69677
Centre Chirurgical Ambroise Paré
Neuilly Sur Seine, France, 92200
La Clinique Pasteur, 45 Avenue de Lombez
Toulouse, France, 31076
Herz-Zentrum Bad Krozingen
Bad Krozingen, Germany, 79189
Klinik für Kardiologie II mit interventioneller Elektrophysiologie
Bad Neustadt/Saale, Germany, 97616
Cardioangiologisches Centrum Bethanien - CCB
Frankfurt, Germany, 60431
Universitätsklinikum Greifswald Elektrophysiologie
Greifswald, Germany, 17475
Asklepios Klinik St. Georg
Hamburg, Germany, 20099
Herz-Zentrum-Bodensee Konstanz
Konstanz, Germany, 78464
Semmelweis University of Medicine, Kardiovaskuläres Zentrum
Budapest, Hungary, 1122
Cardiac Arrhythmia Research Centre Department of Cardiovascular Medicine Centro Cardiologico Monzino University of Milan
Milan, Italy, 20138
Isala Klinieken loc. Weezenlanden Diagram Clinical Resarch
Zwolle, Netherlands, 8011
Hospital Clinic, University of Barcelona
Barcelona, Spain, 08036
Arrhythmia Unit Hospital Clinico San Carlos
Madrid, Spain, 28040
Hospital Universitario Virgen de la Victoria, Department of Cardiology, Campus Teatinos sn
Malaga, Spain, 29010
Hospital Clinico Universtitario, Cardiology Department Arrhythmia Unit
Valencia, Spain, 46014
Universitätsspital Basel, Elektrophysiologie/ Kardiologie
Basel, Switzerland, 4031
Sponsors and Collaborators
Medtronic International Trading Sarl
Principal Investigator: Karl-Heinz Kuck, Prof. Dr. Asklepios Klinikum St. Georg

Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Medtronic International Trading Sarl Identifier: NCT01490814     History of Changes
Other Study ID Numbers: FI-123
First Posted: December 13, 2011    Key Record Dates
Last Update Posted: May 10, 2016
Last Verified: May 2016

Keywords provided by Medtronic International Trading Sarl:
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

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes