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

NCT01490814 | Completed Results DMC

• 1 other identifier: FI-123
• Study Type: interventional
• Target: 769
• Locations: 8 countries
• Sites: 19

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.

Conditions

Symptomatic Paroxysmal Atrial Fibrillation (PAF)

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (2)

Cryoballoon ablation

ACTIVE COMPARATOR

Procedure: Electrical isolation of the pulmonary veins

Radiofrequency ablation

ACTIVE COMPARATOR

Procedure: Electrical isolation of pulmonary veins

Interventions

Electrical isolation of pulmonary veins PROCEDURE

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.

Radiofrequency ablation

Electrical isolation of the pulmonary veins PROCEDURE

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.

Cryoballoon ablation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Medtronic: collaborator
• Medtronic Cardiac Ablation Solutions: lead

Study Sites (19)

Na Homolce Hospital, Cardiology

Prague, 515030, Czechia

Location

Hospital Henri Mondor CHU, Service de Cardiologie

Créteil, 94010, France

Location

CHU Lyon, Départment de Rythmologie, Hospital Cardiologique Pradel

Lyon, 69677, France

Location

Centre Chirurgical Ambroise Paré

Neuilly-sur-Seine, 92200, France

Location

La Clinique Pasteur, 45 Avenue de Lombez

Toulouse, 31076, France

Location

Herz-Zentrum Bad Krozingen

Bad Krozingen, 79189, Germany

Location

Klinik für Kardiologie II mit interventioneller Elektrophysiologie

Bad Neustadt/Saale, 97616, Germany

Location

Cardioangiologisches Centrum Bethanien - CCB

Frankfurt, 60431, Germany

Location

Universitätsklinikum Greifswald Elektrophysiologie

Greifswald, 17475, Germany

Location

Asklepios Klinik St. Georg

Hamburg, 20099, Germany

Location

Herz-Zentrum-Bodensee Konstanz

Konstanz, 78464, Germany

Location

Semmelweis University of Medicine, Kardiovaskuläres Zentrum

Budapest, 1122, Hungary

Location

Cardiac Arrhythmia Research Centre Department of Cardiovascular Medicine Centro Cardiologico Monzino University of Milan

Milan, 20138, Italy

Location

Isala Klinieken loc. Weezenlanden Diagram Clinical Resarch

Zwolle, 8011, Netherlands

Location

Hospital Clinic, University of Barcelona

Barcelona, 08036, Spain

Location

Arrhythmia Unit Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria, Department of Cardiology, Campus Teatinos sn

Málaga, 29010, Spain

Location

Hospital Clinico Universtitario, Cardiology Department Arrhythmia Unit

Valencia, 46014, Spain

Location

Universitätsspital Basel, Elektrophysiologie/ Kardiologie

Basel, 4031, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 25146732 BACKGROUND

• Kuck 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.

  PMID: 27042964 RESULT

• Huang 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.

  PMID: 37071112 DERIVED

• Kuck 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.

  PMID: 29700058 DERIVED

• Chun 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.

  PMID: 28751544 DERIVED

• Kuck 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.

  PMID: 27381589 DERIVED

• Luik 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.

  PMID: 26283655 DERIVED

Related Links

• 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.
• Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.
• FIRE AND ICE: LBCT ACC

Results Point of Contact

• Title: Ralf Meyer
• Organization: Medtronic

ralf.meyer@medtronic.com

+49215981490

Study Officials

• Karl-Heinz Kuck, Prof. Dr.

  Asklepios Klinikum St. Georg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: December 13, 2011
• Study Start: December 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: April 13, 2026
• Results First Posted: November 2, 2018

Record last verified: 2026-03

Locations

NL (1); CZ (1); FR (4); DE (6); ES (4); CH (1); HU (1); IT (1)