Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
This is a prospective, randomized (2:1) multicenter trial to investigate the optimal treatment of Persistent and Longstanding Persistent AF referred for Radiofrequency (RF) ablation.The study objective is to compare the efficacy and safety of two interventional approaches, in preventing the recurrence of AF in symptomatic, drug refractory patients with persistent or longstanding persistent atrial fibrillation.

Official Title
-----------------
Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation

Conditions
-----------------
Atrial Fibrillation, Persistent and Longstanding Persistent Atrial Fibrillation

Intervention / Treatment
-----------------
* Device: AtriCure Bipolar System
* Device: Standard Endocardial Ablation with Catheter
* Device: AtriClip® PRO LAA Exclusion System
* Device: Endocardial Ablation with Catheter
* Device: Repeated Endocardial ablation(s)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has a history of symptomatic Persistent AF and a left atrium (LA) > 4cm or Long Standing Persistent AF as defined by the HRS/EHRA/ECAS expert consensus statement Patient is refractory to or intolerant of at least one antiarrhythmic drug (class I or III) Patient is mentally able and willing to give informed consent Exclusion Criteria: Patient has longstanding persistent AF > 10 years Patient presenting with paroxysmal AF Patient with persistent AF and a LA-diameter ≤ 4cm AF is secondary to electrolyte imbalance, thyroid disease, or other reversible or non-cardiovascular cause Patient underwent previous ablation procedure or heart surgery Patient needs other cardiac surgery procedures besides AF treatment (valve, coronary, others) Contraindication for either catheter ablation or epicardial surgery (including, but not limited to: previous thoracic radiation, previous perimyocarditis, Previous cardiac tamponade, Pleural adhesions, Prior thoracotomy) Body mass index > 35 LA Diameter > 6 cm Left ventricular ejection fraction < 30 % Severe mitral regurgitation (>II) Patient unable to undergo TransEsophageal Echocardiogram (TEE) Presence of LA thrombus by TEE, CT scan, MRI or angiography History of cerebrovascular disease, including stroke or transient ischemic attack (TIA) within 6 months prior to enrollment Active infection or sepsis Other clinical conditions precluding inclusion (e.g., organ disease, disturbances of hemostasis) Contraindication to anticoagulant therapy, or inability to comply with anticoagulant therapy Pregnancy, planned pregnancy or breastfeeding Life expectancy is less than 12 months Patient is involved in another study involving an investigational drug or device

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hybrid Procedure<br>Endoscopic epicardial surgical ablation (first stage) combined with endocardial catheter ablation (second stage) performed between 91 and 180 days post index procedure. | Device: AtriCure Bipolar System<br> <br> Device: AtriClip® PRO LAA Exclusion System<br> <br> Device: Endocardial Ablation with Catheter<br> <br> |
| Active Comparator: Catheter Procedure<br>Standard catheter ablation with pulmonary vein (PV) isolation (minimum lesion set) and optional additional lesions (index procedure). When required due to AF recurrence, ablation may be repeated within 6 months after the index-procedure according to clinical indications and consistent with the Heart Rhythm Society (HRS)/European Heart Rhythm Association (EHRA)/European Cardiac Arrhythmia Society (ECAS) Consensus Statement | Device: Standard Endocardial Ablation with Catheter<br> <br> Device: Repeated Endocardial ablation(s)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects free from documented Atrial Fibrillation (AF), Atrial Flutter (AFL) or Atrial Tachycardia (AT) episodes > 30 seconds in duration through 12 months follow-up, in the absence of Class I or III Antiarrhythmic Drugs (AADs). |  | Through 12-months post the Endocardial procedure (Hybrid Procedure) or last allowed Catheter Ablation(Catheter Procedure) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects free from documented AF, AFL or AT episodes > 30 seconds in duration through 24 and 36 months follow-up, in the absence of Class I or III AADs. |  | Through 24- and 36-months post the Endocardial procedure (Hybrid Procedure) or last allowed Catheter Ablation(Catheter Procedure) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atrial Fibrillation, Persistent and Longstanding Persistent AF, Hybrid Procedure, Catheter Ablation