Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial - Star AF II Study

Study Overview
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Brief Summary
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This investigation is designed with the hypothesis that combined PV Antral Isolation and Ablation of Complex Fractionated Electrograms (PVI+CFE) approach will offer a higher success rate compared to the Wide Circumferential Pulmonary Vein Antrum Isolation (PVI) approach and to the Combined PV Antral Isolation and Empiric Linear Ablation (PVI+Lines) approach.

Official Title
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Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial - Star AF II Study

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: PVI + Lines ablation
* Procedure: PVI
* Procedure: PVI + CFE ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age is18 years or greater; Patients undergoing a first-time ablation procedure for AF; Patients with persistent AF; Persistent AF will be defined as a sustained episode lasting > 7 days and less than 3 years. Patients with symptomatic AF that is refractory to at least one antiarrhythmic medication; At least one episode of persistent AF must have been documented by ECG, holter, loop recorder, telemetry, trans telephonic monitoring (TTM), or implantable device within last 2 years of enrollment in this investigation; Patients must be able and willing to provide written informed consent to participate in this investigation; and Patients must be willing and able to comply with all peri-ablation and follow-up requirements. Exclusion Criteria: Patients with paroxysmal AF; Patients with long-standing persistent AF; Patients for whom cardioversion or sinus rhythm will never be attempted/pursued; Patients with AF felt to be secondary to an obvious reversible cause; Patients with contraindications to systemic anticoagulation with heparin or coumadin or a direct thrombin inhibitor; Patients with left atrial size ≥ 60 mm (2D echocardiography, parasternal long axis view); and Patients who are pregnant.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PVI + Lines Ablation<br> | Procedure: PVI + Lines ablation<br>* Pulmonary vein antrum isolation with additional linear ablation (mitral line and roof line)<br>|
| Active Comparator: PVI Ablation<br> | Procedure: PVI<br>* Pulmonary vein antrum isolation<br>|
| Experimental: PVI + CFE<br> | Procedure: PVI + CFE ablation<br>* Pulmonary vein antrum isolation with additional complex fractionated electrogram ablation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from AF | Freedom from documented AF episodes > 30 seconds at 18 months after one or two ablation procedure with/without antiarrhythmic medications (AAD). In the CT.gov website and in our protocol, we have stated the above primary endpoint (PE). This was the identical PE used in the original STAR AF I study. The intent of this PE was to present the success rates after both 1 procedure and after 2 procedures separately as was done in the original STAR AF I study. However, this is not entirely clear from the way the PE is stated. It may appear that our PE is the success rate after 2 procedures (1 or 2 may imply 2). Since our sample size calculation for the STAR AF II study was based on a single procedure success rate, the single procedure success rate with/without AAD will be used as the PE. The success rate after 2 procedures will be provided as the 1st. secondary endpoint. This clarification is done prior to locking the database and prior to any data analysis. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from atrial arrhythmia | Freedom from documented atrial arrhythmia episodes > 30 seconds at 18 months after one or two ablation procedures with/without antiarrhythmic medications | 18 months | 
| Freedom from atrial flutter and AT | Freedom from documented atrial flutter and atrial tachycardia episodes > 30 seconds at 18 months after one and two procedures with/without antiarrhythmic medications | 18 months | 
| Freedom from documented or not atrial arrhythmia | Freedom from any atrial arrhythmia (documented or not) episodes > 30 seconds at 18 months after one or two ablation procedures with/without antiarrhythmic medications | 18 months | 
| Freedom from symptomatic AF | Freedom from symptomatic AF episodes > 30 seconds at 18 months after one or two ablation procedures with/without antiarrhythmic medications | 18 months | 
| Freedom from symptomatic atrial arrhythmia | Freedom from symptomatic atrial arrhythmia episodes > 30 seconds at 18 months after one or two ablation procedures with/without antiarrhythmic medications | 18 months | 
| Incidence of peri-procedural complications, including stroke, PV stenosis, cardiac perforation, esophageal injury and death | Incidence of peri-procedural complications, including stroke, PV stenosis, cardiac perforation, esophageal injury and death | 18 months | 
| Procedure duration and fluoroscopy time | Procedure duration and fluoroscopy time | 18 months | 
| Number of repeat procedures | Number of repeat procedures | 18 months | 
| Effect of each strategy on AF cycle length/regularity/termination | Effect of each strategy on AF cycle length/regularity/termination | 18 months | 
| Relationship of acute termination of AF to long-term procedural outcome | Relationship of acute termination of AF to long-term procedural outcome | 18 months | 
| Percentage achievement of complete linear block in linear ablation arm | Percentage achievement of complete linear block in linear ablation arm | 18 months | 
| Effect of complete linear block on procedural outcome in linear ablation arm | Effect of complete linear block on procedural outcome in linear ablation arm | 18 months | 
| Quality of life measurements (SF-36, EQ-5D and CCS SAF) | Quality of life measurements (SF-36, EQ-5D and CCS SAF) at baseline, 6, 12 and 18 months after one and/or two ablation procedures | 18 MONTHS | 
| Correlation of AF burden to symptoms and quality of life changes | Correlation of AF burden to symptoms and quality of life changes | 18 Months | 
| Improvement in AF burden by > 90% post ablation procedure | Improvement in AF burden by > 90% post ablation procedure | 18 months | 
| Relationship of ablating all atrial arrhythmias versus ablation of only targeted endpoints on long term outcome | Relationship of ablating all atrial arrhythmias versus ablation of only targeted endpoints on long term outcome | 18 months | 
| Cut off of AF burden that affects the Quality of Life measurement | Cut off of AF burden that affects the Quality of Life measurement | 18 months | 
| Evaluation of cost utility | Evaluation of cost utility | 18 months |