Clinical trial NCT01803438: Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation
Official title: Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases
Keywords: paroxysmal Atrial Fibrillation
Cryoablation
Pulmonary Vein Isolation
Lead sponsor: Medtronic Cardiac Ablation Solutions
Sponsor class: INDUSTRY
First posted: 2013-03-04
Enrollment: 220
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: 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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
  * 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.

Primary outcomes:
measure: Freedom from any atrial arrhythmia recurrence
timeFrame: 12 months
Secondary outcomes:
measure: quality of life
timeFrame: 12 months
measure: Hospital or emergency services accesses
timeFrame: 12 Months
measure: Freedom from occurrence of AF
timeFrame: 12 months
measure: Freedom from occurrence of documented left atrial tachycardia and left atrial flutter
timeFrame: 12 months
measure: Symptomatic palpitations burden
timeFrame: 12 months
measure: Severe adverse events incidence
timeFrame: 12 months
measure: Freedom from persistent AF
timeFrame: 12 months
measure: Echocardiographic left atrial re-modelling
timeFrame: 12 months
measure: health care utilization
timeFrame: 12 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: nstituto Cardiovascular de Buenos Aires
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Brussel
country: Belgium
facility: Heart Rhythm Management Centre, UZ Brussels - VUB Brussel
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Sestre Milosrdnice
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Sestre
city: Amiens
country: France
facility: NCHU Amiens
city: Grenoble
country: France
facility: CHU Grenoble
city: Paris
country: France
facility: CHU La Pitié
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Bad Nauheim
country: Germany
facility: Kerckhoff - Klinik
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum Bethanien
city: Hamburg
country: Germany
facility: Universitätsklinikum Eppendorf
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Munich
country: Germany
facility: Klinikum Bogenhausen
city: Cotignola
country: Italy
facility: Maria Cecilia Hospital
city: Massa
country: Italy
facility: Ospedale S.S. Giacomo e Cristoforo
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bergen
country: Norway
facility: Haukeland Hospital
Study officials:
affiliation: Kerckhoff - Klinik, Bad Nauheim, Germany
name: Malte Kuniss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Rhythm Management Centre, UZ Brussels - VUB Brussel, Belgium
name: GianBattista Chierchia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.