Clinical trial NCT01490814: FIRE AND ICE: Comparative Study of Two Ablation Procedures in Patients With Atrial Fibrillation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Medtronic Atrial Fibrillation Solutions
Sponsor class: INDUSTRY
Collaborators: name: Medtronic
First posted: 2011-12-13
Enrollment: 769
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: 33 months
measure: 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.
timeFrame: 33 months
Secondary outcomes:
measure: All-cause Death
timeFrame: 33 months
measure: Arrhythmia-related Death
timeFrame: 33 months
measure: Total Procedure Duration
timeFrame: Through the initial ablation procedure
measure: Total Time of Fluoroscopy
timeFrame: Fluoroscopy meter time through the initial ablation procedure
measure: Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.
timeFrame: 33 months
measure: Number of Cardiovascular Hospitalizations
timeFrame: 33 months
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Na Homolce Hospital, Cardiology
city: Créteil
country: France
facility: Hospital Henri Mondor CHU, Service de Cardiologie
city: Lyon
country: France
facility: CHU Lyon, Départment de Rythmologie, Hospital Cardiologique Pradel
city: Neuilly Sur Seine
country: France
facility: Centre Chirurgical Ambroise Paré
city: Toulouse
country: France
facility: La Clinique Pasteur, 45 Avenue de Lombez
city: Bad Krozingen
country: Germany
facility: Herz-Zentrum Bad Krozingen
city: Bad Neustadt/Saale
country: Germany
facility: Klinik für Kardiologie II mit interventioneller Elektrophysiologie
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum Bethanien - CCB
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald Elektrophysiologie
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Konstanz
country: Germany
facility: Herz-Zentrum-Bodensee Konstanz
city: Budapest
country: Hungary
facility: Semmelweis University of Medicine, Kardiovaskuläres Zentrum
city: Milan
country: Italy
facility: Cardiac Arrhythmia Research Centre Department of Cardiovascular Medicine Centro Cardiologico Monzino University of Milan
city: Zwolle
country: Netherlands
facility: Isala Klinieken loc. Weezenlanden Diagram Clinical Resarch
city: Barcelona
country: Spain
facility: Hospital Clinic, University of Barcelona
city: Madrid
country: Spain
facility: Arrhythmia Unit Hospital Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria, Department of Cardiology, Campus Teatinos sn
city: Valencia
country: Spain
facility: Hospital Clinico Universtitario, Cardiology Department Arrhythmia Unit
city: Basel
country: Switzerland
facility: Universitätsspital Basel, Elektrophysiologie/ Kardiologie
Study officials:
affiliation: Asklepios Klinikum St. Georg
name: Karl-Heinz Kuck, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.