Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation

Study Overview
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Brief Summary
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This study examines non-inferiority of pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) to extensive ablation; and reveals the effect of the presence or origin of AF trigger on outcomes of catheter ablation.

Detailed Description
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Study design The EARNEST-PVI trial is a prospective, multicenter, randomized, open-label non-inferiority trial in which patients with persistent AF will undergo ablation. After providing written informed consent at each hospital, patients who are eligible for the trial will be randomized to either PVI alone or PVI plus additional ablation. Left atrial dimensions will be the only adjustment factor considered in dynamic allocation to avoid bias. Patients randomized to the PVI alone group will be treated with PVI, while patients randomized to the PVI plus additional ablation group will receive additional complex fractionated atrial electrogram or linear ablation after PVI. Ablation for AF triggers from non-PV foci, the cavotricuspid isthmus, clinical coexisting tachyarrhythmia such as atrial flutter (AFL), atrial tachycardia (AT), and supraventricular tachycardia will be allowed in both groups. Patients will be followed up 1, 3, 6, 9, and 12 months after the procedure. The primary endpoint of the study is the recurrence of AF documented by scheduled or symptom-driven ECG during 1 year after the procedure. Recurrence of AF is defined as the documentation of any atrial arrhythmia including AF, AFL, and/or AT lasting ≥ 30 seconds by ECG or other appropriate tests. The sample size and randomization are specified based on the concept of non-inferiority to achieve the primary objective. The recurrence rate of AF was assumed to be 40% in both groups and a non-inferiority margin of 10% was calculated by referring to the previous studies. Therefore, a sample size of 256 subjects in each group is required with a power of 80% and significance level of 5% considering some dropouts. The statistical evaluation will be carried out according to the intention-to-treat principle.

Official Title
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A Multicenter, Randomized Controlled, Non-inferiority Trial Investigating Efficacy and Safety of Pulmonary Vein Isolation Alone for Recurrence Prevention Compared to Extensive Ablation in Patients With Persistent Atrial Fibrillation

Conditions
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Atrial Fibrillation, Catheter Ablation, Recurrence

Intervention / Treatment
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* Procedure: PVI
* Procedure: PVI plus additional ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing a first-time ablation procedure for persistent AF Exclusion Criteria: Patients with long-standing persistent AF lasting ≥ 5 years Patients with left atrial dimension ≥ 50 mm by 2-dimensional echocardiography Patients with valvular AF (defined as the presence of mitral or aortic stenosis or regurgitation with a history of rheumatic fever or implantation of artificial heart valves) Patients who underwent prior cardiac surgery Patients receiving hemodialysis Patients with heart failure (left ventricular ejection fraction < 30% and NYHA class ≥ III) Patients receiving antiarrhythmic agents before the ablation procedure (within 60 days for amiodarone, or 5 half-lives for other drugs) Patients who are not considered to be suitable candidates by the attending physician

Ages Eligible for Study
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Minimum Age: 20 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: PVI alone<br>PVI, and ablation for AF triggers from non-PV foci, the cavotricuspid isthmus, clinical coexisting tachyarrhythmia such as atrial flutter (AFL), atrial tachycardia (AT), and supraventricular tachycardia, if necessary | Procedure: PVI<br>* Ipsilateral circumferential PVI is the recommended PVI strategy. The success of PVI is defined as the achievement of the dissociation of PV potentials in all PVs. Disappearance of PV potentials is reconfirmed at the end of the procedure, a minimum of 20 minutes after the initial success of PVI.<br>|
| Placebo Comparator: PVI plus additional ablation<br>PVI, additional CFAE or linear ablation after PVI, and ablation for AF triggers from non-PV foci, the cavotricuspid isthmus, clinical coexisting tachyarrhythmia such as atrial flutter (AFL), atrial tachycardia (AT), and supraventricular tachycardia, if necessary | Procedure: PVI plus additional ablation<br>* In addition to PVI, CFAE ablation, linear ablation, or both; the choice of which is decided by the physician<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence of AF documented by scheduled or symptom-driven ECG during 1 year after the procedure | Recurrence of AF is defined as the documentation of any atrial arrhythmia including AF, AFL, and/or AT lasting ≥ 30 seconds by ECG or other appropriate tests. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular events | death (and/or cause of death), or symptomatic cerebral infarction | 1 year | 
| The effect of the presence or absence of AF trigger foci | recurrence of AF according to the presence or absence of AF trigger foci | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent atrial fibrillation, non-inferiority trial