Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart DiseasesPhase 4NCT01803438

Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation

A Phase 4 study testing cryoballoon ablation system and Antiarrhythmic Drugs in people with Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases, run by Medtronic Cardiac Ablation Solutions at 19 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the effectiveness of Pulmonary Vein Isolation (PVI) performed with the Arctic Front™ Advance Cardiac CryoAblation Catheter System as first-line therapy in comparison with antiarrhythmic drugs (AAD) in patients with paroxysmal atrial fibrillation (AF). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases
What is being tested?: cryoballoon ablation system and Antiarrhythmic Drugs
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 220 participants
Where: 19 sitesin 9 countries
Study dates: Jun 2014to 20 Jan 2020
Phase: Phase 4
Are there results?: None posted in the registry

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

Subject has been diagnosed with symptomatic paroxysmal atrial fibrillation as defined above and at least two symptomatic episodes in the last six months prior to inclusion.
At least one episode of AF must be documented during the prior year by any kind of ECG recording.
Subject has structural normal heart with an LVEF ≥ 50%, thickness of the inter-ventricular septum ≤12 mm and left atrium diameters (short axis) < 46 mm obtained by transthoracic echocardiography.
Subject has normal ECG parameters (QRS width in the 12 channel surface ECG ≤120 ms, QTc - interval < 440 ms, PQ - interval ≤ 210 ms; all parameters should be measured at sinus rhythm).
Subject is at least 18 and not older than 75years old.
Subject is able and willing to give informed consent.

Who cannot join

Subject developed persistent AF at least once in history (electrical or pharmacological cardioversion after 48h or episode duration >7 days).
Subject has documented typical atrial flutter.
Subject has any history of successful or unsuccessful treatment of AF with class I or III antiarrhythmic or sotalol with the intention to prevent an AF recurrence. Patients pretreated with above AAD at maximum 48 hours with the intention to convert an AF episode are allowed.
Subject had any previous left atrial ablation.
Subject had any previous cardiac surgery, e.g. prosthetic valves.
Subject has permanent pacemaker or defibrillator implant.

Show all 34Show fewer

Subject has 2° type II, 3° degree AV-block or left/right bundle branch block pattern.
Subject has unstable angina pectoris.
Subject has history of previous myocardial infarction or percutaneous intervention during the last three months.
Subject has symptomatic carotid stenosis.
Subject has chronic obstructive pulmonary disease with detected pulmonary hypertension or any other evidence of significant lung disease.
Subject has any contraindication for oral anticoagulation.
Subject has any history of previous transient ischemic attack or stroke.
Subject has known intra-cardiac thrombus formation.
Subject has any significant congenital heart defect corrected or not (except for patent foramen ovale that is allowed).
Subject has evidence of congestive heart failure (NYHA class II, III or IV) in sinus rhythm.
Subject has hypertrophic cardiomyopathy.
Subject has abnormal long or short QT interval, signs of Brugada syndrome, known inheriting ion channel disease on the family, arrhythmogenic right ventricular dysplasia.
Subject has sarcoidosis.
Subject has pulmonary vein stent.
Subject has myxoma. Exclusion criteria based on laboratory abnormalities
Subject has thrombocytosis (platelet count > 600,000 / μl) or thrombocytopenia (platelet count <100,000 / μl).
Subject has any untreated or uncontrolled hyperthyroidism or hypothyroidism.
Subject has renal dysfunction with glomerular filtration rate < 60 ml / min.
Subject has known cryoglobulinaemia. General exclusion criteria
Subject has a reversible causes for AF like hyperthyroidism and alcoholism.
Subject is a pregnant woman or woman of childbearing potential not on adequate birth control: only woman with a highly effective method of contraception [oral contraception or intra-uterine device] (who must have a negative pregnancy test within 1 week of the start of the therapy) or sterile woman can be enrolled.
Subject is a breastfeeding woman.
Subject has an active systemic infection.
Subject is employed by Medtronic or by the department of any of the investigators or is a close relative of any of the investigators.
Subject is unwilling or unable to comply fully with study procedures and follow-up due to any disease condition, which can raise doubt about compliance and influencing the study outcome especially any kind of cancer, severe bleeding in history or a suspected pro-coagulant state.
Legal incapacity or evidence that a subject cannot understand the purpose and risks of the study or inability to comply fully with study procedures and follow up.
Subject has a life expectancy of ≤ 1 year.
Subject is currently enrolled or planning to participate in a potentially confounding drug or device trial during the course of this study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from the Medtronic study manager.

Trial locations and contacts

19 sites in 9 countries.

Country

City, postcode or hospital

19 sites in 9 countries

Germany5 sites

Kerckhoff - Klinik
Bad Nauheim
Cardioangiologisches Centrum Bethanien
Frankfurt, 60431
Universitätsklinikum Eppendorf
Hamburg, 20246
Westpfalz-Klinikum GmbH
Kaiserslautern, 67655
Klinikum Bogenhausen
Munich

Other trials in Germany

France4 sites

NCHU Amiens
Amiens
CHU Grenoble
Grenoble
CHU La Pitié
Paris
CHU Charles Nicolle
Rouen

Other trials in France

Croatia2 sites

Klinicki bolnicki centar Sestre Milosrdnice
Zagreb
Klinicki bolnicki centar Sestre
Zagreb

Other trials in Croatia

Italy2 sites

Maria Cecilia Hospital
Cotignola, 48033
Ospedale S.S. Giacomo e Cristoforo
Massa

Other trials in Italy

Netherlands2 sites

Catharina Ziekenhuis
Eindhoven, 5623 EJ
Erasmus MC
Rotterdam

Other trials in Netherlands

Argentina1 site

nstituto Cardiovascular de Buenos Aires
Buenos Aires, C1428

Other trials in Argentina

Australia1 site

Monash Medical Centre
Melbourne

Other trials in Australia

Belgium1 site

Heart Rhythm Management Centre, UZ Brussels - VUB Brussel
Brussels

Other trials in Belgium

Norway1 site

Haukeland Hospital
Bergen

Other trials in Norway

About this study

Official title: Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation.

Conditions: Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases
Being tested: cryoballoon ablation system, Antiarrhythmic Drugs
Keywords: paroxysmal Atrial Fibrillation, Cryoablation, Pulmonary Vein Isolation
Medical subject headings: Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cryoballoon ablation systemDevice
Antiarrhythmic DrugsDrug
AAD therapy based on hospital clinical practice according to ESC Guidelines 2012

Study groups in NCT01803438
Study group	Role	What they receive
AADs	Active comparator	AAD therapy based on hospital clinical practice according to ESC Guidelines 2012 Receives: Drug: Antiarrhythmic Drugs
Cryoablation procedure	Experimental	electrical pulmonary veins isolation performed with cryoballoon ablation system Receives: Device: cryoballoon ablation system

What is being measured

The primary outcome is the main question the study is designed to answer.

Freedom from any atrial arrhythmia recurrence
The primary endpoint is freedom from any atrial arrhythmia recurrence at 12 months (at least one episode of AF, atrial flutter or atrial tachycardia with a duration > 30 seconds documented by 7 day Holter ECG or any other printed ECG recording following a blanking period or a dosing optimizing period of 3 months).
Measured: 12 months

Secondary outcomes (9)

quality of life
The quality of life of the two arms measured by means of SF-36 Health Survey and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaires will be compared at 12 months follow-up.
Measured: 12 months
Hospital or emergency services accesses
Hospital or emergency services accesses due to symptoms caused by documented atrial arrhythmias will be compared in the two arms at 12 months follow-up.
Measured: 12 Months
Freedom from occurrence of AF
Freedom from occurrence of AF (after 3 months blanking period) will be compared between the two arms at 12 months follow-up.
Measured: 12 months
Freedom from occurrence of documented left atrial tachycardia and left atrial flutter
Freedom from occurrence of documented left atrial tachycardia and typical - or atypical left atrial flutter (after 3 months blanking period or AAD optimization period) will be compared between the two arms at 12 months follow-up.
Measured: 12 months
Symptomatic palpitations burden
Symptomatic palpitations burden will be evaluated by mean of Patient's diary information and compared between the two arms at 12 months follow-up.
Measured: 12 months
Severe adverse events incidence
Severe adverse events incidence will be compared between the two arms during the whole course of the study.
Measured: 12 months
Freedom from persistent AF
Freedom from persistent AF (AF episode lasting longer than 7 days or interrupted by pharmacological or electrical cardioversion after 48h from the onset of the episode) will be compared between the two arms at 12 months follow-up.
Measured: 12 months
Echocardiographic left atrial re-modelling
Echocardiographic left atrial parameters will be compared between the two arms at 6 and 12 months follow ups.
Measured: 12 months
health care utilization
Frequency, type and associated cost of health care utilization and utility will be compared between the two arms at 12 months follow-up.
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201420 Jan 2020

First posted4 Mar 2013 (estimated)
Study startJun 2014
Primary completion16 Oct 2019
Study completion20 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart DiseasesStudies of the same condition, open and under way.
More trials run by Medtronic Cardiac Ablation SolutionsThe sponsor's other registered studies.
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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 220 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01803438
Sponsor's protocol ID: Cryo-FIRST
Status last verified: Feb 2025
First submitted: 1 Mar 2013
Last updated: 13 Feb 2025
Results posted: No
Data monitoring committee: Yes

Publications

Andrade JG, Moss JWE, Kuniss M, Sadri H, Wazni O, Sale A, Ismyrloglou E, Chierchia GB, Kaplon R, Mealing S, Bainbridge J, Bromilow T, Lane E, Khaykin Y. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation. Can J Cardiol. 2024 Apr;40(4):576-584. doi: 10.1016/j.cjca.2023.11.019. Epub 2023 Nov 23.
PubMed 38007219
Pavlovic N, Chierchia GB, Velagic V, Hermida JS, Healey S, Arena G, Badenco N, Meyer C, Chen J, Iacopino S, Anselme F, Dekker L, Scazzuso F, Packer DL, de Asmundis C, Pitschner HF, Piazza FD, Kaplon RE, Kuniss M; Cryo-FIRST Investigators. Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms. Am Heart J. 2021 Dec;242:103-114. doi: 10.1016/j.ahj.2021.08.007. Epub 2021 Sep 8.
PubMed 34508694

Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation.
ClinicalTrials.gov ID: NCT01803438
Acronym / sponsor ID: Cryo-FIRST
Conditions: Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases
Keywords: paroxysmal Atrial Fibrillation, Cryoablation, Pulmonary Vein Isolation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 220 participants (actual)
Lead sponsor: Medtronic Cardiac Ablation SolutionsIndustry (pharma, biotech, devices)
Study start: Jun 2014
Primary completion: 16 Oct 2019 (actual)
Study completion: 20 Jan 2020 (actual)
First posted: 4 Mar 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
AADs	Active comparator	Drug: Antiarrhythmic DrugsAAD therapy based on hospital clinical practice according to ESC Guidelines 2012
Cryoablation procedure	Experimental	Device: cryoballoon ablation systemelectrical pulmonary veins isolation performed with cryoballoon ablation system

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Subject has been diagnosed with symptomatic paroxysmal atrial fibrillation as defined above and at least two symptomatic episodes in the last six months prior to inclusion.
At least one episode of AF must be documented during the prior year by any kind of ECG recording.
Subject has structural normal heart with an LVEF ≥ 50%, thickness of the inter-ventricular septum ≤12 mm and left atrium diameters (short axis) < 46 mm obtained by transthoracic echocardiography.
Subject has normal ECG parameters (QRS width in the 12 channel surface ECG ≤120 ms, QTc - interval < 440 ms, PQ - interval ≤ 210 ms; all parameters should be measured at sinus rhythm).
Subject is at least 18 and not older than 75years old.

Key exclusion criteria (34 listed)

Subject developed persistent AF at least once in history (electrical or pharmacological cardioversion after 48h or episode duration >7 days).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
cryoballoon ablation system	Device	Cryoablation procedure
Antiarrhythmic DrugsAAD therapy based on hospital clinical practice according to ESC Guidelines 2012	Drug	AADs

Primary outcome

Freedom from any atrial arrhythmia recurrence
Time frame: 12 months
The primary endpoint is freedom from any atrial arrhythmia recurrence at 12 months (at least one episode of AF, atrial flutter or atrial tachycardia with a duration > 30 seconds documented by 7 day Holter ECG or any other printed ECG recording following a blanking period or a dosing optimizing period of 3 months).

9 secondary outcomes

quality of life
Time frame: 12 months
Hospital or emergency services accesses
Time frame: 12 Months
Freedom from occurrence of AF
Time frame: 12 months
Freedom from occurrence of documented left atrial tachycardia and left atrial flutter
Time frame: 12 months
Symptomatic palpitations burden
Time frame: 12 months
Severe adverse events incidence
Time frame: 12 months
Freedom from persistent AF
Time frame: 12 months
Echocardiographic left atrial re-modelling
Time frame: 12 months
health care utilization
Time frame: 12 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
Derived from this study: PubMed 38007219Andrade JG, Moss JWE, Kuniss M, Sadri H, Wazni O, Sale A, Ismyrloglou E, Chierchia GB, Kaplon R, Mealing S, Bainbridge J, Bromilow T, Lane E, Khaykin Y. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation. Can J Cardiol. 2024 Apr;40(4):576-584. doi: 10.1016/j.cjca.2023.11.019. Epub 2023 Nov 23.
Derived from this study: PubMed 34508694Pavlovic N, Chierchia GB, Velagic V, Hermida JS, Healey S, Arena G, Badenco N, Meyer C, Chen J, Iacopino S, Anselme F, Dekker L, Scazzuso F, Packer DL, de Asmundis C, Pitschner HF, Piazza FD, Kaplon RE, Kuniss M; Cryo-FIRST Investigators. Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms. Am Heart J. 2021 Dec;242:103-114. doi: 10.1016/j.ahj.2021.08.007. Epub 2021 Sep 8.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Malte Kuniss, MD principal investigator

Kerckhoff - Klinik, Bad Nauheim, Germany

GianBattista Chierchia, MD principal investigator

Heart Rhythm Management Centre, UZ Brussels - VUB Brussel, Belgium

19 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Germany, France, Croatia, Italy, Netherlands and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Freedom from any atrial arrhythmia recurrence (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01803438, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.