Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation (EARNEST-PVI)

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

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.

Study Overview

• Status: Unknown
• Conditions: Recurrence; Atrial Fibrillation; Catheter Ablation
• Intervention / Treatment: Procedure: PVI; Procedure: PVI plus additional ablation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PVI alone; 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; 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.
Placebo Comparator: PVI plus additional ablation; 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; In addition to PVI, CFAE ablation, linear ablation, or both; the choice of which is decided by the physician

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Osaka Cardiovascular Conference
• Investigators: Principal Investigator: Yasushi Sakata, MD, PhD, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine

Publications and helpful links

General Publications

• Sato T, Sotomi Y, Hikoso S, Nakatani D, Mizuno H, Okada K, Dohi T, Kitamura T, Sunaga A, Kida H, Oeun B, Egami Y, Watanabe T, Minamiguchi H, Miyoshi M, Tanaka N, Oka T, Okada M, Kanda T, Matsuda Y, Kawasaki M, Masuda M, Inoue K, Sakata Y; Osaka Cardio Vascular Conference (OCVC)-Arrhythmia Investigators *. DR-FLASH Score Is Useful for Identifying Patients With Persistent Atrial Fibrillation Who Require Extensive Catheter Ablation Procedures. J Am Heart Assoc. 2022 Aug 16;11(16):e024916. doi: 10.1161/JAHA.121.024916. Epub 2022 Aug 5.
• Curran L, Nah G, Marcus GM, Tseng Z, Crawford MH, Parikh NI. Clinical Correlates and Outcomes of Methamphetamine-Associated Cardiovascular Diseases in Hospitalized Patients in California. J Am Heart Assoc. 2022 Aug 16;11(16):e023663. doi: 10.1161/JAHA.121.023663. Epub 2022 Aug 1.
• Inoue K, Hikoso S, Masuda M, Furukawa Y, Hirata A, Egami Y, Watanabe T, Minamiguchi H, Miyoshi M, Tanaka N, Oka T, Okada M, Kanda T, Matsuda Y, Kawasaki M, Hayashi K, Kitamura T, Dohi T, Sunaga A, Mizuno H, Nakatani D, Sakata Y; OCVC Arrhythmia Investigators. Pulmonary vein isolation alone vs. more extensive ablation with defragmentation and linear ablation of persistent atrial fibrillation: the EARNEST-PVI trial. Europace. 2021 Apr 6;23(4):565-574. doi: 10.1093/europace/euaa293.

Helpful Links

• UMIN-CTR

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2016
• Primary Completion (Anticipated): March 31, 2019
• Study Completion (Anticipated): March 31, 2019

Study Registration Dates

• First Submitted: April 20, 2018
• First Submitted That Met QC Criteria: April 20, 2018
• First Posted (Actual): May 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 2, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Persistent atrial fibrillation; non-inferiority trial
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Recurrence
• Other Study ID Numbers: 14377-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No