A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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This study (STOP AF) is a prospective, randomized, controlled, multicenter, pivotal clinical investigation conducted at 26 investigational sites in the United States and Canada. Subjects with paroxysmal atrial fibrillation (PAF) referred for ablative intervention after efficacy failure of one or more Study Atrial Fibrillation (AF) Drugs (flecainide, propafenone or sotalol) were randomized 2:1 to cryoablation intervention (Experimental Subjects, ES) or to a Study AF Drug (Control Subjects, CS). Subjects were followed for 12 months with scheduled and symptom-driven assessments to detect recurrent atrial fibrillation by means of periodic electrocardiograms, weekly scheduled trans-telephonic monitoring, patient-initiated trans-telephonic monitoring, and 24-hour Holter monitoring at 6 and 12 months. The first 90 days after study therapy was initiated was considered a blanked period for all subjects.

Detailed Description
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STOP AF (PS-023) is a randomized, controlled study of subjects 18 to 75 years old who had been referred for ablative intervention after failing one or two (but not all three) anti-arrhythmic drugs used in the treatment of AF (flecainide, propafenone and sotalol). Study subjects were randomized into two arms: the cryoablation (treatment) arm and the membrane-active antiarrhythmic drug (control) arm. A 90- day blanked follow-up period, including reablation and medication adjustments was applied in both arms to optimize therapies. All subjects underwent follow-up assessments at 1, 3, 6, 9 and 12 months, weekly transtelephonic monitoring, 24-hour Holter monitoring and CT/MRI of the pulmonary veins(at 6 and 12 months) during the trial period. Control subjects who were confirmed to be chronic treatment failures were permitted to crossover to cryoablation in this trial. Acute procedural success was defined for subjects that underwent cryoablation and demonstrated electrical isolation in ≥ 3 Pulmonary Veins (PVs) at the conclusion of the first protocol-defined cryoablation procedure using the Arctic Front® Cardiac CryoAblation Catheter System. The primary effectiveness endpoint was defined as having acute procedural success and freedom from chronic treatment failure (CTF) for experimental subjects, and freedom from CTF for control subjects. Freedom from (CTF) was defined for both groups as the occurrence of detectable AF during a non-blanked follow-up period, or an AF Intervention, or the use of a non-study AF drug at any time. The co-primary safety outcome measures were Cryoablation Procedure Events (CPEs) in cryoablated subjects and Major Atrial Fibrillation Events (MAFEs) in both groups. CPEs were device- or procedure-related serious adverse events. Other safety assessments were made during the course of the STOP AF trial specific to pulmonary vein stenosis (PVS) and phrenic nerve injury.

Official Title
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A Randomized, Controlled Clinical Trial of Catheter Cryoablation in the Treatment of Paroxysmal Atrial Fibrillation.

Conditions
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Paroxysmal Atrial Fibrillation

Intervention / Treatment
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* Device: Arctic Front® Cryoablation Catheter
* Drug: Flecainide or Sotalol or Propafenone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented Paroxysmal Atrial Fibrillation (PAF): PAF diagnosis, 2 episodes of PAF within the last 2 months, at least 1 episode of PAF must be documented Age 18-75 Documented Effectiveness Failure of one (1) AF drug Willing to be randomized to either group and do full 12 month follow-up Able to follow standardized AF drug protocol Exclusion Criteria: Any cardioversion within 3 months or more than 2 within 2 years Amiodarone within 6 months LA size > 5.0cm Previous LA ablation/surgery, structural heart disease, heart failure class III or IV Hypertrophic cardiomyopathy, Mitral prosthesis Unstable angina, uncontrolled hyperthyroidism Stroke or TIA within 6 months, MI within 2 months, cardiac surgery within 3 months Thrombocytosis, thrombocytopenia Any condition contraindicating chronic anticoagulation EF <40% Pregnancy Life expectancy <1year

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 |
| --- | --- |
| Experimental: Experimental<br>Experimental subjects received cryoablation intended to isolate the pulmonary veins and ablate arrhythmia foci. If necessary, experimental subjects were allowed a previously failed Study Atrial Fibrillation Drug (AF Drug). | Device: Arctic Front® Cryoablation Catheter<br>* Experimental Subjects received cryoablation intended to isolate the pulmonary veins and ablate arrhythmia foci with the cryoablation catheter system.<br>* Other names: Artic Front®;|
| Active Comparator: Control<br>Control Subjects were treated with an AF Drug (flecainide, propafenone, or sotalol) that they had not previously failed. | Drug: Flecainide or Sotalol or Propafenone<br>* Flecainide 200 mg / day Propafenone 450 mg / day Propafenone-SR 650 mg / day Sotalol 240 mg / day<br>* Other names: Propafenone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Procedural Success (APS) | Acute Procedural Success was defined as a demonstration of electrical isolation in ≥ 3 Pulmonary Veins (PVs) at the conclusion of the first protocol-defined cryoablation procedure. APS was decided at the end of the procedure the mean time was calculated for the time frame. | 371.4 Minutes (Average) | 
| Freedom From Chronic Treatment Failure (CTF) | Subjects that did not have or were free of CTF. CTF was defined as the occurence of an Atrial Fibrillation (AF) intervention, use of non-study AF drug therapy, or the occurence of detectable AF which is is defined as an episode of AF, documented in a tracing, and lasting more than 30 seconds, occurring during a Non Blanked Follow-up Period. | 12 month follow up period | 
| Treatment Success | Treatment Success was defined as Acute Procedure Success (APS) and freedom from Chronic Treatment Failure (CTF) for Experimental Subjects, and freedom from CTF for Control Subjects. Under this pre-specified definition of Treatment Success, Experimental Subjects must have had APS and remained free of CTF during the 12-month follow-up duration, while Control Subjects must have remained free of CTF during the 12-month follow-up duration. | 12 months | 
| Freedom From Major Atrial Fibrillation Events (MAFEs) | Subjects that did not have or were free of MAFEs. MAFEs were serious adverse events categorized as cardiovascular death, myocardial infarction, stroke, or hospitalization for AF recurrence/ablation, flutter ablation, embolic events, heart failure, hemorrhage or anti-arrhythmic drug treatment. | 12 Months | 
| Cryoablation Procedure Events (CPEs) | Subjects that had CPEs. CPEs were device- or procedure-related serious adverse events (SAE) categorized as access site complications, cardiac damage, pulmonary vein (PV) stenosis, embolic complications, arrhythmias, unresolved phrenic nerve palsy and death. | To end of ablation procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation