Using Cryoballoon Ablation as Initial Treatment for Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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This study is to assess the effectiveness and safety of using cryoballoon ablation comparing with anti-arrhythmic drug therapy as initial treatment for naive patients with persistent atrial fibrillation.

Detailed Description
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Subjects with persistent atrial fibrillation with no history of treatment with anti-arrhythmic drugs are randomized 1:1 to either an anti-arrhythmic drug or pulmonary vein isolation using the cryoballoon catheter.

Official Title
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Using Cryoballoon Ablation as Initial Treatment for Patients With Persistent Atrial Fibrillation Comparing to Anti-arrhythmic Drugs

Conditions
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Atrial Fibrillation, Persistent, Arrhythmias, Cardiac

Intervention / Treatment
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* Drug: Antiarrhythmic drug including Propafenone, Sotalol, Dronedarone and Amiodarone
* Device: cryoballoon ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of symptomatic persistent AF: Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by consecutive ECG recordings OR Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by an ECG recording and one doctor note indicating patient had symptoms consistent with AF Age 18 or older (or older than 18 if required by local law) Structurally normal heart with LVEF ≥50%, interventricular septum thickness ≤ 12 mm, and left atrial diameter <46 mm (short axis) as obtained by transthoracic echocardiography. • Normal ECG parameters when measured in sinus rhythm (QRS width ≤120 ms in a 12-channel surface ECG, QTc interval <440 ms, and PQ interval ≤210 ms). Exclusion Criteria: History of AF treatment with class I or III antiarrhythmic drug, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode are allowed. left atrial ablation or surgical procedure (including left atrial appendage closures) Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function) within 12 months Presence of any pulmonary vein stents Presence of any pre-existing pulmonary vein stenosis Pre-existing hemidiaphragmatic paralysis Presence of any cardiac valve prosthesis +3 and +4 mitral valve regurgitation or stenosis Any cardiac surgery, myocardial infarction, percutaneous coronary intervention (PCI) / percutaneous transluminal coronary angioplasty (PTCA) or coronary artery stenting which occurred during the 3 month interval preceding e consent date Unstable angina New York Heart Association (NYHA) Class II, III or IV congestive heart failure Primary pulmonary hypertension Rheumatic heart disease Thrombocytosis, thrombocytopenia Any condition contraindicating chronic anticoagulation Active systemic infection Hypertrophic cardiomyopathy Cryoglobulinemia Uncontrolled hyperthyroidism Any cerebral ischemic event (strokes or transient ischemic attacks (TIAs)) which occurred during the 6 month interval preceding the consent date Any woman known to be pregnant or breastfeeding. Life expectancy less than one year Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic Active intracardiac thrombus Known drug or alcohol dependency Unwilling or unable to comply fully with study procedures and follow-up Significant Chronic Kidney Disease-estimated Glomerular Filtration Rate(CKD-eGFR) <30umol/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug treatment group<br>receive class I or class III AAD to restore or maintain sinus rhythm. | Drug: Antiarrhythmic drug including Propafenone, Sotalol, Dronedarone and Amiodarone<br>* Class I or III antiarrhythmic drug, including sotalol<br>|
| Experimental: cryoballoon ablation group<br>receive cryoballoon ablation to restore sinus rhythm. | Device: cryoballoon ablation<br>* Pulmonary vein isolation by cryoballoon ablation using Medtronic Arctic Front Advance™ Cardiac CryoAblation Catheters (23mm and 28mm)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success at 12 months | Treatment success at 12 months after antiarrhythmic drug (AAD) initiation or ablation utilizing cryoballoon catheter measured by freedom from AF recurrence following a 3-month period after the index ablation or AAD initiation. | Randomization to 12 months | 
| Rate of serious adverse events | Rate of serious procedure-related and serious cryoablation system-related reported adverse events through 12 months after the index ablation procedure | Randomization to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life changes at 12 months measured by AFEQT | The improvement in quality of life between baseline and 12 months after the index ablation procedure or AAD measured by AF Quality of Life Survey (AFEQT) | one year | 
| Quality of life changes at 12 months measured by SF-12 | The improvement in quality of life between baseline and 12 months after the index ablation procedure or AAD measured by 12-Item Short Form Survey (SF-12) | one year | 
| Arrhythmia recurrence during blanking period | atrial tachycardia recurrence rate during the blanking period | 3 months | 
| time to first time cardiovascular hospitalization (month) | time to first time cardiovascular hospitalization after treatment (month) | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cryoablation, pulmonary vein isolation, atrial fibrillation, Anti-Arrhythmic Agents