STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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To provide data demonstrating the safety and effectiveness of the Arctic Front Advance™ Cardiac CryoAblation Catheter for the treatment of recurrent symptomatic paroxysmal atrial fibrillation, without the requirement that the subjects be drug refractory.

Detailed Description
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Subjects with paroxysmal 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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STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation

Conditions
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Atrial Fibrillation, Atrial Fibrillation New Onset

Intervention / Treatment
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* Device: Cryoablation
* Drug: Antiarrhythmic drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of symptomatic paroxysmal AF with the following documentation: (1) physician's note indicating recurrent self- terminating AF or paroxysmal AF; and (2) any ECG documented AF within 6 months prior to enrollment. Age 18-80 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. Prior persistent AF (cardioversion after 48 hours or continuous AF that is sustained >7 days) Left atrial diameter greater than 5.0 cm Prior left atrial ablation or left atrial surgical procedure 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) Body mass index (BMI) >35 kg/m2 Presence of any pulmonary vein stents Known presence of any pre-existing pulmonary vein stenosis Pre-existing hemidiaphragmatic paralysis Presence of any cardiac valve prosthesis Moderate or severe mitral valve regurgitation or stenosis Any cardiac surgery, myocardial infarction, percutaneous coronary intervention/ percutaneous transluminal coronary angioplasty or coronary artery stenting which occurred during the 90 day interval preceding the date the subject signed the Informed Consent Form Unstable angina New York Heart Association (NYHA) class III or IV congestive heart failure and/or known left ventricular ejection fraction (LVEF) less than 45% Diagnosis of primary pulmonary hypertension Rheumatic heart disease Thrombocytosis, thrombocytopenia Contraindication to anticoagulation therapy Active systemic infection Hypertrophic cardiomyopathy Cryoglobulinemia Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, obstructive sleep apnea, and acute alcohol toxicity. Any cerebral ischemic event (strokes or transient ischemic attacks) which occurred during the 180 day interval preceding the date the subject signed the Informed Consent Form, or any known unresolved complications from previous stroke/transient ischemic attack Existing thrombus Pregnancy Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of this study not pre-approved by Medtronic Patients with contraindications to a Holter monitor Unwilling or unable to comply fully with study procedures and follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Anti-arrhythmic drug<br> | Drug: Antiarrhythmic drug<br>* Antiarrhythmic drug initiation<br>|
| Experimental: Cryoablation<br> | Device: Cryoablation<br>* Pulmonary vein isolation via ablation with cryoballoon catheter<br>* Other names: ArcticFront Advance Cardiac CryoAblation Catheter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter. | Treatment success after AAD initiation (control arm) or pulmonary vein isolation ablation procedure utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter (treatment arm). Treatment success is the opposite of treatment failure. Treatment failure was defined as any of the following: Acute procedural failure (treatment arm only). Documented AF/AT/AFL on ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm). Minimum of 30 seconds on ambulatory monitoring or 10 seconds on 12-lead ECG. Any subsequent AF surgery or ablation in the left atrium. Any subsequent cardioversion after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm). Class I or III antiarrhythmic drug (or sotalol) use after the 90-day blanking period (treatment arm only). | Randomization to 12 months | 
| Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events. | Measured by rate of composite list of serious adverse events in cryoablation-treated as randomized arm. Includes: TIA within 7 days Cerebrovascular accident within 7 days Major bleed that requires transfusion or results in a 20% or greater fall in hematocrit (HCT) within 7 days Development of a significant pericardial effusion within 30 days. (One that results in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in a 1-cm or more pericardial effusion as documented by echocardiography). Symptomatic PV stenosis within 12 months; accompanied by one of the following: 50%-75% reduction in diameter of the pulmonary vein, with symptoms not explained by other conditions; OR >75% reduction in diameter of the pulmonary vein MI within 7 days PNI unresolved at 12 months AE fistula within 12 months Major vascular complication that requires intervention, prolongs hospital stay, or requires hospital admission (within 7 days). | Randomization to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Scores at Baseline Compared to 12 Months | There are two hypotheses tested in the objective, with separate hypothesis tests for (1) the difference in composite scores from the AFEQT questionnaire taken at baseline and 12 month visits, and (2) for the difference in composite scores for the EQ-5D questionnaire taken at baseline and 12-month visits. Composite AFEQT score is on a scale of zero to one hundred. Higher scores are better. Composite EQ-5D score is on a scale of zero to one. Higher scores are better. | Baseline and 12 Months | 
| Healthcare Utilization | Compare health care utilization between the treatment and control arms. There are two hypotheses tested in the objective, with separate hypothesis tests for: (1) the rate of total health care utilization events (cardiovascular-related hospitalizations, emergency room visits, or unscheduled office visits) over 12 months shown as freedom from cardiovascular health care utilization by treatment arm, and (2) freedom from cardioversions (electrical or pharmacological) over 12 months by treatment arm. | Initial treatment through 12 months. |