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

• ClinicalTrials.gov Identifier: NCT01803438
• Recruitment Status: Completed
• First Posted: March 4, 2013
• Last Update Posted: February 25, 2020
• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Collaborator: Medtronic Atrial Fibrillation Solutions
• Information provided by (Responsible Party): Medtronic Cardiac Rhythm and Heart Failure

Tracking Information

• First Submitted Date: March 1, 2013
• First Posted Date: March 4, 2013
• Last Update Posted Date: February 25, 2020
• Study Start Date: June 2014
• Actual Primary Completion Date: October 16, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2013)

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 1, 2013)

• quality of life [ Time Frame: 12 months ]
  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.
• Hospital or emergency services accesses [ Time Frame: 12 Months ]
  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.
• Freedom from occurrence of AF [ Time Frame: 12 months ]
  Freedom from occurrence of AF (after 3 months blanking period) will be compared between the two arms at 12 months follow-up.
• Freedom from occurrence of documented left atrial tachycardia and left atrial flutter [ Time Frame: 12 months ]
  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.
• Symptomatic palpitations burden [ Time Frame: 12 months ]
  Symptomatic palpitations burden will be evaluated by mean of Patient's diary information and compared between the two arms at 12 months follow-up.
• Severe adverse events incidence [ Time Frame: 12 months ]
  Severe adverse events incidence will be compared between the two arms during the whole course of the study.
• Freedom from persistent AF [ Time Frame: 12 months ]
  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.
• Echocardiographic left atrial re-modelling [ Time Frame: 12 months ]
  Echocardiographic left atrial parameters will be compared between the two arms at 6 and 12 months follow ups.
• health care utilization [ Time Frame: 12 months ]
  Frequency, type and associated cost of health care utilization and utility will be compared between the two arms at 12 months follow-up.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Symptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart Diseases

Intervention

• Device: cryoballoon ablation system
• Drug: Antiarrhythmic Drugs
  AAD therapy based on hospital clinical practice according to ESC Guidelines 2012

Study Arms

• Active Comparator: AADs
  AAD therapy based on hospital clinical practice according to ESC Guidelines 2012
  Intervention: Drug: Antiarrhythmic Drugs
• Experimental: Cryoablation procedure
  electrical pulmonary veins isolation performed with cryoballoon ablation system
  Intervention: Device: cryoballoon ablation system

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2019): 220
• Original Estimated Enrollment (submitted: March 1, 2013): 218
• Actual Study Completion Date: January 20, 2020
• Actual Primary Completion Date: October 16, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Croatia, France, Germany, Italy, Netherlands, Norway

Administrative Information

• NCT Number: NCT01803438
• Other Study ID Numbers: Cryo-FIRST
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• Original Responsible Party: Medtronic Bakken Research Center
• Current Study Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Original Study Sponsor: Medtronic Bakken Research Center
• Collaborators: Medtronic Atrial Fibrillation Solutions

Investigators

• Principal Investigator: Malte Kuniss, MD; Kerckhoff - Klinik, Bad Nauheim, Germany
• Principal Investigator: GianBattista Chierchia, MD; Heart Rhythm Management Centre, UZ Brussels - VUB Brussel, Belgium

• PRS Account: Medtronic Cardiac Rhythm and Heart Failure
• Verification Date: February 2020