A Prospective Study of Medical Therapy Against Cryoballoon Ablation in Symptomatic Recent Onset Persistent AF

Study Overview
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Brief Summary
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Prospective trial comparing the efficacy and safety of CryoBalloonAblation (CBA) to standardized medication for treatment of early onset persistent atrial fibrillation (AF) without structural heart disease. The value of CBA in these patients has never been studied; the endpoints for persistent patients are much easier than for paroxysmal patients. Reduction in left atrial (LA) size will be compared versus patients on drug therapy and versus failing patients.

Detailed Description
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The total AF history should be shorter than 24 months. Symptomatic patients can be included if they have had within the last year at least 2 episodes of documented AF, lasting minimal 30 sec. One episode in the entire history should have lasted more than 48 h, requiring electrical or pharmacological cardioversion or stopped spontaneously after more than 7 days. All patients eligible for the study will sign informed consent, have an echocardiogram prior to inclusion to exclude severe left ventricular dysfunction, to rule out significant valve abnormalities, left ventricular hypertrophy and to assess the LA volume and diameter. Prior to randomization, and after inclusion it is suggested to the local investigators to perform an MRI-scan or CT scan of the LA and pulmonary veins (in both branches of the study ) in eligible patients to assess the anatomy and the left atrial volume. The results should not influence the strategy of treatment.

Official Title
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A Prospective Study of Medical Therapy Against Cryoballoon Ablation in Symptomatic Recent Onset Persistent Atrial Fibrilation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: single ablation (CryoBalloonAblation (CBA)
* Drug: sequential drug adjustment (propafenone, sotalol or flecainide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 21 years and legally capable First documentation or history of symptomatic AF more than 30 sec within the last 2 years Twice AF within the last year One episode cardioverted after more than 48 hours or spontaneously terminated after more than 7 days Eligible for at least one first step drug therapy (sotalol, propafenone, or flecainide) and for amiodarone Left ventricular ejection fraction estimated > 45% LA diameter < 50 mm (parasternal short axis) and LA volume less than 100 ml (apical view, Area Length method;) CHADS2 ≤ 2 Failed AAD strategy, or untreated with AAD No use of Amiodarone in the previous 3 months (except IV or oral for 7 days) Informed consent Exclusion Criteria: Age > 75 yrs CHF Ischemic heart disease as known in the history (Severe) Left ventricular hypertrophy as shown on echo (IVSd or PWd > 14 mm) Hyperthyroidism Congenital heart disease Hypertrophic Cardiomyopathy, Arrhythmogenic Right ventricular Cardiomyopathy, channelopathies Contra-indications to AAD Long QT syndrome Received already adequately dosed all level 1 drugs (sotalol, propafenone, and flecainide) Pure (typical) atrial flutter as documented on one occasion

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Experimental: Cryoablation<br>Cryoballoon single ablation (as described in the reference) at entry after randomization to this group. Single procedure,not to be repeated. | Device: single ablation (CryoBalloonAblation (CBA)<br>* Cryoablation at entry, after randomization to this group<br>|
| Active Comparator: Drug<br>Conventional, available anti arrhythmic drugs (propafenone, sotalol or flecainide), in a first stage, sequential, with amiodarone in second stage | Drug: sequential drug adjustment (propafenone, sotalol or flecainide)<br>* Correct drug dosage at entry, sequential adjustment / titration, in stage 2 amiodarone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sinus rhythm | Sinus rhythm at one year | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction LA volume | Reduction left atrial volume in successfully treated patients | one year | 
| Number of cardioversions | Number of cardioversions | one year | 
| Percentage on anti arrhythmic drugs (AAD) | Percentage on AAD in each group | 6 months | 
| Percentage on AAD | Percentage on AAD in each group | 12 months | 
| Vascular complications | Vascular complications, including tamponade | one year | 
| Stroke, transient ischemic attack (TIA) | Stroke, TIA (symptomatic) | one year | 
| Serious adverse events (SAE) | Adverse events leading to admission or death | one year | 
| Freedom of AF | Freedom of atrial fibrillation with all means | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, cryoablation, catheter ablation