Symptomatic Paroxysmal Atrial Fibrillation (PAF)NCT01490814
FIRE AND ICE: Comparative Study of Two Ablation Procedures in Patients With Atrial Fibrillation
A study testing Electrical isolation of the pulmonary veins and Electrical isolation of pulmonary veins in people with Symptomatic Paroxysmal Atrial Fibrillation (PAF), run by Medtronic Cardiac Ablation Solutions at 19 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Symptomatic Paroxysmal Atrial Fibrillation (PAF)
- What is being tested?
- Electrical isolation of the pulmonary veins and Electrical isolation of pulmonary veins
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 769 participants
- Where
- 19 sitesin 8 countries
- Study dates
- Dec 2011to Jan 2016
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- 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.
- 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).
Trial locations and contacts
19 sites in 8 countries.
19 sites in 8 countries
Germany6 sites
Herz-Zentrum Bad Krozingen
Bad Krozingen, 79189
Klinik für Kardiologie II mit interventioneller Elektrophysiologie
Bad Neustadt/Saale, 97616
Cardioangiologisches Centrum Bethanien - CCB
Frankfurt, 60431
Universitätsklinikum Greifswald Elektrophysiologie
Greifswald, 17475
Asklepios Klinik St. Georg
Hamburg, 20099
Herz-Zentrum-Bodensee Konstanz
Konstanz, 78464
France4 sites
Hospital Henri Mondor CHU, Service de Cardiologie
Créteil, 94010
CHU Lyon, Départment de Rythmologie, Hospital Cardiologique Pradel
Lyon, 69677
Centre Chirurgical Ambroise Paré
Neuilly-sur-Seine, 92200
La Clinique Pasteur, 45 Avenue de Lombez
Toulouse, 31076
Spain4 sites
Hospital Clinic, University of Barcelona
Barcelona, 08036
Arrhythmia Unit Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario Virgen de la Victoria, Department of Cardiology, Campus Teatinos sn
Málaga, 29010
Hospital Clinico Universtitario, Cardiology Department Arrhythmia Unit
Valencia, 46014
Hungary1 site
Semmelweis University of Medicine, Kardiovaskuläres Zentrum
Budapest, 1122
Italy1 site
Cardiac Arrhythmia Research Centre Department of Cardiovascular Medicine Centro Cardiologico Monzino University of Milan
Milan, 20138
Netherlands1 site
Isala Klinieken loc. Weezenlanden Diagram Clinical Resarch
Zwolle, 8011
Switzerland1 site
Universitätsspital Basel, Elektrophysiologie/ Kardiologie
Basel, 4031
About this study
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
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.
Read the 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.
- Being tested
- Electrical isolation of the pulmonary veins, Electrical isolation of pulmonary veins
- Keywords
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrical isolation of the pulmonary veinsProcedure or surgery
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.
Electrical isolation of pulmonary veinsProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Cryoballoon ablation | Active comparator | Not described Receives: Procedure: Electrical isolation of the pulmonary veins |
| Radiofrequency ablation | Active comparator | Not described Receives: Procedure: Electrical isolation of pulmonary veins |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 33 months
Secondary outcomes (6)
All-cause Death
Measured: 33 months
Arrhythmia-related Death
Measured: 33 months
Total Procedure Duration
Measured: Through the initial ablation procedure
Total Time of Fluoroscopy
Measured: Fluoroscopy meter time through the initial ablation procedure
Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.
Measured: 33 months
Number of Cardiovascular Hospitalizations
The total number of cardiovascular hospitalizations reported over the duration of the study.
Measured: 33 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Symptomatic Paroxysmal Atrial Fibrillation (PAF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 769 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic Cardiac Ablation Solutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medtronic
- Responsible party
- Sponsor
- Investigators
- Karl-Heinz Kuck, Prof. Dr., Principal investigator, Asklepios Klinikum St. Georg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490814
- Sponsor's protocol ID
- FI-123
- Status last verified
- Mar 2026
- First submitted
- 6 Dec 2011
- Last updated
- 13 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Furnkranz A, Brugada J, Albenque JP, Tondo C, Bestehorn K, Wegscheider K, Ouyang F, Kuck KH. Rationale and Design of FIRE AND ICE: A multicenter randomized trial comparing efficacy and safety of pulmonary vein isolation using a cryoballoon versus radiofrequency ablation with 3D-reconstruction. J Cardiovasc Electrophysiol. 2014 Dec;25(12):1314-20. doi: 10.1111/jce.12529. Epub 2014 Nov 12.
PubMed 25146732Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.
PubMed 27042964Huang C, Wang J, He C, Yang K, Zhao H, Chen J, Su L. The Efficacy and Safety of Cryoballoon Versus Radiofrequency Ablation for the Treatment of Atrial Fibrillation: A Meta-Analysis of 15 International Randomized Trials. Cardiol Rev. 2024 Nov-Dec 01;32(6):546-553. doi: 10.1097/CRD.0000000000000531. Epub 2024 Oct 4.
PubMed 37071112Kuck KH, Brugada J, Furnkranz A, Chun KRJ, Metzner A, Ouyang F, Schluter M, Elvan A, Braegelmann KM, Kueffer FJ, Arentz T, Albenque JP, Kuhne M, Sticherling C, Tondo C; FIRE AND ICE Investigators. Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation. Circ Arrhythm Electrophysiol. 2018 May;11(5):e006204. doi: 10.1161/CIRCEP.118.006204.
PubMed 29700058Chun KRJ, Brugada J, Elvan A, Geller L, Busch M, Barrera A, Schilling RJ, Reynolds MR, Hokanson RB, Holbrook R, Brown B, Schluter M, Kuck KH; FIRE AND ICE Investigators. The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation on Healthcare Utilization and Costs: An Economic Analysis From the FIRE AND ICE Trial. J Am Heart Assoc. 2017 Jul 27;6(8):e006043. doi: 10.1161/JAHA.117.006043.
PubMed 28751544Kuck KH, Furnkranz A, Chun KR, Metzner A, Ouyang F, Schluter M, Elvan A, Lim HW, Kueffer FJ, Arentz T, Albenque JP, Tondo C, Kuhne M, Sticherling C, Brugada J; FIRE AND ICE Investigators. Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. Eur Heart J. 2016 Oct 7;37(38):2858-2865. doi: 10.1093/eurheartj/ehw285. Epub 2016 Jul 5.
PubMed 27381589Luik A, Radzewitz A, Kieser M, Walter M, Bramlage P, Hormann P, Schmidt K, Horn N, Brinkmeier-Theofanopoulou M, Kunzmann K, Riexinger T, Schymik G, Merkel M, Schmitt C. Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation: The Prospective, Randomized, Controlled, Noninferiority FreezeAF Study. Circulation. 2015 Oct 6;132(14):1311-9. doi: 10.1161/CIRCULATIONAHA.115.016871. Epub 2015 Aug 17.
PubMed 26283655