Hybrid AbLaTion of Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
A randomised controlled trial to assess the efficacy of staged hybrid ablation when compared with standard catheter ablation in patients with non-paroxysmal atrial fibrillation (AF)

Detailed Description
-----------------
The objective of this randomized study is to evaluate the safety and efficacy of Convergent hybrid ablation when compared to standard catheter ablation in patients with non-paroxysmal AF. Patients will be randomised in a 1:1 ratio. The primary efficacy endpoint will be freedom from persistent atrial arrhythmia (measured from the end of a 3-month blanking period up to 24 months (12 and 24 months).

Official Title
-----------------
A Randomised Controlled Trial Comparing Hybrid Convergent Ablation to Standard Catheter Ablation in Patients With Non-Paroxysmal Atrial Fibrillation

Conditions
-----------------
Persistent Atrial Fibrillation, Atrial Fibrillation, Persistent, Atrial Arrhythmia, Atrial Fibrillation

Intervention / Treatment
-----------------
* Device: AtriCure EPi-Sense-AF Guided Coagulation System +/- Atriclip
* Device: Endocardial Catheter Ablation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Persistent or Long-standing Persistent AF Dilated left atrium Suitable for either procedure Exclusion Criteria: Unable to provide written consent Previous open-heart surgery Active infection, oesophageal ulcer stricture or oesophageal varices Prior catheter ablation of atrial fibrillation (prior ablation for atrial flutter / supraventricular tachycardia or ventricular arrhythmia acceptable) Contraindication to anticoagulation, or active thrombus in left atrium despite therapeutic anticoagulation Severe valvular heart disease Unstable coronary artery disease Uncontrolled ventricular arrhythmia Heart attack or stroke within the last 90 days Pregnant, breast-feeding, or women of childbearing age who plan to get pregnant within six months Severe concomitant condition or presence of an implanted device that would preclude the patient from undergoing trial procedures

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

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clinical study. 1:1 randomised. Convergent Hybrid Ablation Procedure versus standalone endocardial catheter ablation).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convergent Hybrid Ablation with Left Atrial Appendage Exclusion<br>Staged Convergent Hybrid Ablation Procedure Stage 1 - Minimally-Invasive Surgical Epicardial Ablation Procedure +/- concomitant LAA exclusion. Stage 2 - Endocardial Catheter Ablation | Device: AtriCure EPi-Sense-AF Guided Coagulation System +/- Atriclip<br>* Minimally-invasive epicardial ablation +/- left atrial appendage exclusion using an epicardial clip, combined with endocardial radiofrequency catheter ablation<br>* Other names: Convergent Hybrid Epicardial Endocardial Ablation Procedure with concomitant left atrial appendage exclusion;Device: Endocardial Catheter Ablation<br>* Standard percutaneous endocardial catheter ablation of atrial fibrillation<br>* Other names: Percutaneous Catheter Ablation;|
| Active Comparator: Standard Endocardial Catheter Ablation<br>Standard endocardial catheter ablation | Device: Endocardial Catheter Ablation<br>* Standard percutaneous endocardial catheter ablation of atrial fibrillation<br>* Other names: Percutaneous Catheter Ablation;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from persistent atrial arrhythmia after a single procedure (either the completed hybrid ablation or catheter ablation) off Class I or III medications | Recurrence of persistent atrial arrhythmia during follow-up months). | Measured from the end of a 3-month blanking period at 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint | Safety endpoint of severe and non-severe complications as defined in the protocol | Measured as early (within 30- days) and late (> 30 days) after each procedure or part of procedure | 
| Freedom from any atrial arrhythmia lasting > 30 seconds after a single completed procedure on class I/III medications | Recurrence of any atrial arrhythmia > 30 seconds on or off class I / III medications, considering any repeat ablation procedures | Measured from the end of a 3- month blanking period at 12 and 24 months | 
| Freedom from atrial arrhythmias after any redo procedures (on or off class I or III medications) | Recurrence of any atrial arrhythmia > 30 seconds on or off class I / III medications, considering any repeat ablation procedures | Measured from the end of a 3- month blanking period at 12 and 24 months | 
| To assess left ventricular structural remodelling and change in ventricular function in response to either procedure | Left ventricular ejection fraction as recorded on transthoracic echocardiography (TTE) | Pre-procedure and at 12 and 24 months post-procedure | 
| To assess left atrial remodelling in response to either technique. | Left atrial size on Echocardiography | Pre-procedure andat 12 and 24 months post-procedure | 
| To evaluate the effects of the interventions on the patient's symptoms and quality of life (EHRA Score) | Change in European Heart Rhythm Association (EHRA) AF Symptom score | Pre-procedure and at 12 and 24 months post-procedure | 
| To evaluate the effects of the interventions on the patient's symptoms and quality of life (NYHA Class). | Change in New York Heart Association (NYHA) class | Pre-procedure and at 12 and 24 months post-procedure | 
| To evaluate the effects of the interventions on the patient's quality of life (EQ5D) | Change in EuroQol Quality of life Score (EQ5D) | Pre-procedure and at 12 and 24 months post-procedure | 
| To evaluate the effects of the interventions on the patient's quality of life (AFEQT) | Change in Atrial Fibrillation Effect on Quality of Life Score (AFEQT) | Pre-procedure and at 12 and 24 months post-procedure |