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

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.

Atul Verma, David E. Haines, Lucas V.A. Boersma, Nitesh Sood, Andrea Natale et al. (16 authors)

Circulation2023-03-06471 citations

10.1161/circulationaha.123.063988

Electrophysiology lab efficiency comparison between cryoballoon and point-by-point radiofrequency ablation: a German sub-analysis of the FREEZE Cohort study.

Metzner A, Straube F, Tilz RR, Kuniss M, Noelker G, Tebbenjohanns J, Andresen D, Wieneke H, Stellbrink C, Franke J, Dorwarth U, Carion PL, Holbrook R, Hochadel M, Senges J, Hoffmann E, Kuck KH, FREEZE Cohort Study Investigators.

2023-01-098 citations

10.1186/s12872-022-03015-8

Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation

Karl‐Heinz Kück, Josép Brugada, Alexander Fürnkranz, K. R. Julian Chun, Andreas Metzner et al. (16 authors)

Circulation Arrhythmia and Electrophysiology2018-04-26120 citations

10.1161/circep.118.006204

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

K. R. Julian Chun, Josép Brugada, Arif Elvan, László Gellér, M. Busch et al. (14 authors)

Journal of the American Heart Association2017-07-2859 citations

10.1161/jaha.117.006043

Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial

Karl-Heinz Kuck, Alexander Fürnkranz, K. R. Julian Chun, Andreas Metzner, Feifan Ouyang et al. (15 authors)

European Heart Journal2016-07-05343 citations

10.1093/eurheartj/ehw285

Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation

Karl-Heinz Kuck, Josép Brugada, Alexander Fürnkranz, Andreas Metzner, Feifan Ouyang et al. (12 authors)

New England Journal of Medicine2016-04-041,880 citations

10.1056/nejmoa1602014

Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation

Armin Luik, Andrea Radzewitz, Meinhard Kieser, Marlene Walter, Peter Bramlage et al. (14 authors)

Circulation2015-08-17265 citations

10.1161/circulationaha.115.016871

Interventions

PROCEDUREElectrical 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.

PROCEDUREElectrical 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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	—
Number of Cardiovascular Hospitalizations	33 months	The total number of cardiovascular hospitalizations reported over the duration of the study.

Countries

Czechia, France, Germany, Hungary, Italy, Netherlands, Spain, Switzerland

Contacts

PRINCIPAL_INVESTIGATORKarl-Heinz Kuck, Prof. Dr.

Asklepios Klinikum St. Georg

Participant flow

Pre-assignment details

769 subjects were enrolled; 7 subjects exited prior to randomization, 762 were randomized

Participants by arm

Arm	Count
Cryoballoon Ablation 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.	374
Radiofrequency Ablation 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.	376
Total	750

Baseline characteristics

Characteristic	Cryoballoon Ablation	Radiofrequency Ablation	Total
Age, Continuous	59.9 years STANDARD_DEVIATION 9.8	60.1 years STANDARD_DEVIATION 9.2	60.0 years STANDARD_DEVIATION 9.5
Sex: Female, Male Female	153 Participants	140 Participants	293 Participants
Sex: Female, Male Male	221 Participants	236 Participants	457 Participants
Years since first PAF diagnosis	4.6 years STANDARD_DEVIATION 5.1	4.7 years STANDARD_DEVIATION 5.3	4.6 years STANDARD_DEVIATION 5.2

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
other Total, other adverse events	0 / 374	0 / 376
serious Total, serious adverse events	129 / 374	158 / 376

Outcome results

Primary

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.

Time frame: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Cryoballoon Ablation	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.	Death	2 Participants
Cryoballoon Ablation	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.	Atrial Arrhythmia	8 Participants
Cryoballoon Ablation	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.	All-cause stroke or TIA	2 Participants
Cryoballoon Ablation	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.	Non-arrhythmia-related Serious Adverse Event	28 Participants
Cryoballoon Ablation	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.	No primary safety event	334 Participants
Radiofrequency Ablation	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.	Non-arrhythmia-related Serious Adverse Event	36 Participants
Radiofrequency Ablation	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.	No primary safety event	325 Participants
Radiofrequency Ablation	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.	Death	0 Participants
Radiofrequency Ablation	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.	All-cause stroke or TIA	2 Participants
Radiofrequency Ablation	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.	Atrial Arrhythmia	13 Participants

Primary

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

Time frame: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cryoballoon Ablation	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	138 Participants
Radiofrequency Ablation	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	143 Participants

Secondary

All-cause Death

Time frame: 33 months

Population: Subjects randomized and received ablation. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cryoballoon Ablation	All-cause Death	2 Participants
Radiofrequency Ablation	All-cause Death	0 Participants

Secondary

Arrhythmia-related Death

Time frame: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cryoballoon Ablation	Arrhythmia-related Death	0 Participants
Radiofrequency Ablation	Arrhythmia-related Death	0 Participants

Secondary

Number of Cardiovascular Hospitalizations

The total number of cardiovascular hospitalizations reported over the duration of the study.

Time frame: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (NUMBER)
Cryoballoon Ablation	Number of Cardiovascular Hospitalizations	139 number of cardiovascular hospitalization
Radiofrequency Ablation	Number of Cardiovascular Hospitalizations	203 number of cardiovascular hospitalization

Secondary

Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.

Time frame: 33 months

Population: Subjects randomized and received an ablation procedure. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cryoballoon Ablation	Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.	89 Participants
Radiofrequency Ablation	Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.	135 Participants

Secondary

Total Procedure Duration

Time frame: Through the initial ablation procedure

Population: Subjects randomized and received ablation. Modified intent-to-treat (mITT) population.

Arm	Measure	Value (MEAN)	Dispersion
Cryoballoon Ablation	Total Procedure Duration	124.4 minutes	Standard Deviation 39
Radiofrequency Ablation	Total Procedure Duration	140.9 minutes	Standard Deviation 54.9

Secondary

Total Time of Fluoroscopy

Time frame: Fluoroscopy meter time through the initial ablation procedure

Population: Subjects randomized and received ablation procedure. Modified intent-to-treat (mITT) population

Arm	Measure	Value (MEAN)	Dispersion
Cryoballoon Ablation	Total Time of Fluoroscopy	16.6 minutes	Standard Deviation 17.8
Radiofrequency Ablation	Total Time of Fluoroscopy	21.7 minutes	Standard Deviation 13.9

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Contacts

Participant flow

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

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.

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

All-cause Death

Arrhythmia-related Death

Number of Cardiovascular Hospitalizations

Number of Subjects Reporting a Cardiovascular Hospitalization Over the Duration of the Study.

Total Procedure Duration

Total Time of Fluoroscopy