PLEA: Posterior Wall And Left Atrial Appendage Empiric Electrical Isolation for Non-Paroxysmal Atrial Fibrillation

Sponsor

Montefiore Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04216667

Collaborator

Biosense Webster, Inc. (Industry)

932

Enrollment

Locations

Arms

88.5

Anticipated Duration (Months)

58.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of empirical posterior wall isolation (PWI), left atrial appendage electrical isolation (LAAEI) and coronary sinus isolation (CSI) when compared to pulmonary vein isolation (PVI) alone:

PVI alone,
PVI + PWI,
PVI + PWI + LAAEI,
PVI + PWI + LAAEI + CSI.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Procedure: Catheter ablation	N/A

Detailed Description

The Posterior Wall and/or Left Atrial Appendage Empiric Electrical Isolation for Non-Paroxysmal Atrial Fibrillation (The PLEA Trial) is a prospective multicenter randomized controlled study that has the overall goal of establishing the efficacy and safety of different ablation techniques for patients with persistent and long-standing persistent atrial fibrillation. The PLEA trial is designed to test the hypothesis whether posterior wall isolation (PWI) with pulmonary vein isolation (PVI), PWI plus left atrial appendage electrical isolation (LAAEI) with PVI and PWI plus LAAEI plus coronary sinus isolation (CSI) with PVI is superior to the standard approach alone (i.e. PVI alone) in decreasing the incidence of the composite endpoint of all-cause mortality and all-atrial arrhythmia recurrences.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

932 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A total of 932 patients will be randomized with equal allocation to one of four treatment groups. This sample size provides 90% power to detect pairwise differences in response rates between groups ranging from 0.12 to 0.15 based on two-tailed 0.05 level intention to treat chi-squared tests. Specifically, the response rates under the alternative upon which sample size is determined are 0.45, 0.60, 0.75, 0.87 for PVI alone, PVI + PWI, PVI + PWI + LAAEI and PVI + PWI + LAAEI + CSI respectively.A total of 932 patients will be randomized with equal allocation to one of four treatment groups. This sample size provides 90% power to detect pairwise differences in response rates between groups ranging from 0.12 to 0.15 based on two-tailed 0.05 level intention to treat chi-squared tests. Specifically, the response rates under the alternative upon which sample size is determined are 0.45, 0.60, 0.75, 0.87 for PVI alone, PVI + PWI, PVI + PWI + LAAEI and PVI + PWI + LAAEI + CSI respectively.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

The nature of the ablation procedures precludes blinding of physicians to patient treatment. However, patients will be blinded to their ablation strategy (single-blind design) and endpoint assessment will be made by blinded adjudicators from an independent core laboratory.

Primary Purpose:

Treatment

Official Title:

Posterior Wall And Left Atrial Appendage Empiric Electrical Isolation for Non-Paroxysmal Atrial Fibrillation (The PLEA Trial)

Actual Study Start Date :

Jan 16, 2020

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PVI Pulmonary vein isolation alone will be performed using radiofrequency energy	Procedure: Catheter ablation Catheter ablation
Experimental: PVI + PWI Pulmonary vein isolation plus posterior wall isolation will be performed using radiofrequency energy	Procedure: Catheter ablation Catheter ablation
Experimental: PVI + PWI + LAAEI Pulmonary vein isolation plus posterior wall isolation plus left atrial appendage electrical isolation will be performed using radiofrequency energy	Procedure: Catheter ablation Catheter ablation
Experimental: PVI + PWI + LAAEI + CSI Pulmonary vein isolation plus posterior wall isolation plus left atrial appendage electrical isolation plus coronary sinus isolation will be performed using radiofrequency energy	Procedure: Catheter ablation Catheter ablation

Outcome Measures

Primary Outcome Measures

Freedom from documented AF/AT/AFL episodes and all-cause mortality after initial procedure [12 months]
The primary effectiveness endpoint is defined as the freedom from documented AF/AT/AFL episodes (> 30 seconds) and all-cause mortality within 12 months after one ablation procedure without antiarrhythmic medications after blanking period (3 months after ablation) as adjudicated by the independent Core Laboratory. Atrial Fibrillation (AF) Atrial Tachycardia (AT) Atrial Flutter (AFL)
A composite of thromboembolic events, myocardial perforation, pulmonary vein stenosis, atrioesophageal fistula, left and right phrenic nerve paralysis, and other serious adverse events within 12 months post-procedure. [12 months]
The primary safety endpoint is defined as a composite of thromboembolic events, myocardial perforation, pulmonary vein stenosis, atrioesophageal fistula, left and right phrenic nerve paralysis, and other serious adverse events within 12 months post-procedure.

Secondary Outcome Measures

Incidence of peri-procedural and 12-month post procedural complications. [12, 24 and 60 months]
These complications include: ischemic stroke, pulmonary veins (PVs) stenosis, cardiac perforation, esophageal injury, phrenic nerve paralysis, rehospitalization, and death.
AF/AT/AFL Burden [12, 24 and 60 months]
Atrial fibrillation (AF), atrial tachycardia (AT) and/or atrial flutter (AFL) burden at 12 months after single and redo procedures
All-cause mortality [12, 24 and 60 months]
Death from all causes will be assessed
Atrial contractility [6 months]
Myocardial strain will be used to assess atrial contractility after catheter ablation
Heart failure analysis [12, 24 and 60 months]
Primary outcome will be assessed base on left ventricular ejection fraction (LVEF)
Cardiovascular hospitalizations [12, 24 and 60 months]
Cardiovascular hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.
Procedure duration and fluoroscopy time [Day of Procedure]
These times will be compared amongst groups
Number of repeat procedures [12 months]
Number of repeat procedures within 12 months after the first ablation procedure
Cost-effectiveness analysis [12 months]
The CEA will examine the cost of health care resources and health outcomes from the ablation procedure to 1-year postoperatively. The costs will include all health care utilization during this time. Health care utilization, and associated costs, related to the patients' condition, the procedure and adverse events will be the basis of a sensitivity analysis.
Long-term follow-up at 24 and 60 months to evaluate freedom of documented AF/AT/AFL episodes (>30 seconds) and all-cause mortality adjudicated by the Core Laboratory [24 and 60 months]
Freedom from documented AF/AT/AFL episodes (> 30 seconds) and all-cause mortality within 24 and 60 months after one ablation procedure without antiarrhythmic medications after blanking period (3 months after ablation) as adjudicated by the independent Core Laboratory. Atrial Fibrillation (AF) Atrial Tachycardia (AT) Atrial Flutter (AFL)
Freedom from documented AF/AT/AFL episodes (>30 seconds) and all-cause mortality within 12 months after redo ablation procedure. [12 months]
Freedom from all-atrial arrhythmias recurrence (AF/atrial flutter [AFL]/atrial tachycardia [AT]) (episodes >30 seconds on 12-lead ECG, event monitor, Zio patch, Holter or device interrogation) and all-cause mortality (patients who die before the 12-month assessment or who are too ill to undergo assessment of AF are considered not to have response to treatment) during the evaluation period at 12 months after redo-ablation procedures as adjudicated by the independent Core Laboratory.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18 or greater
In good general health as evidenced by medical history and diagnosed with symptomatic persistent AF or long-standing persistent AF.
Persistent AF will be defined as a sustained episode lasting > 7 days and less than 1 year.
Long-standing persistent AF will be defined as a sustained episode lasting more than 1 year and less than 10 years.
Symptoms may include, but are not restricted to, palpitations, shortness of breath, chest pain, fatigue, left ventricular dysfunction, or other symptoms, or any combination of the above.
At least one episode of persistent AF must have been documented by ECG, Holter, loop recorder, ziopatch, telemetry, trans telephonic monitoring (TTM), or implantable device within last 10 years of enrollment in this investigation.
Patients undergoing first time procedure for AF.

Exclusion Criteria:

Patients with paroxysmal AF.

• Paroxysmal AF will be defined as a sustained episode lasting < 7 days (either terminated spontaneously or with pharmacological or electrical cardioversion.

Reversible causes of AF.
Patients with contraindications to systemic anticoagulation with heparin or coumadin, direct thrombin inhibitor or factor Xa inhibitors.
Patients with left atrial size ≥ 75 mm (2D echocardiography, parasternal long axis view)
Left atrial or LAA thrombus
Patients with severe valvular heart disease or after mitral valve replacement (bioprosthetic or mechanical).
Patients with a life expectancy ≤ 24 months
CHA2DS2Vasc score of 0 for men and CHA2DS2Vasc score of 1 for women.
Patients who are pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Grandview Medical Center	Birmingham	Alabama	United States	35243
2	MarinHealth Medical Center	Larkspur	California	United States	94904
3	University of Colorado	Boulder	Colorado	United States	80309
4	Miami Cardiac & Vascular Institute	Miami	Florida	United States	33176
5	Indiana University	Bloomington	Indiana	United States	47405
6	Montefiore Medical Center	Bronx	New York	United States	10467
7	WakedMed Heart & Vascular	Raleigh	North Carolina	United States	27610
8	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
9	Texas Cardiac Arrhythmia Institute	Austin	Texas	United States	78705
10	Baylor Heart Clinic	Houston	Texas	United States	77030
11	Instituto Cardiovascular Adventista	Buenos Aires		Argentina
12	Incor - HCFMUSP	Sao Paulo		Brazil
13	University CES	Medellín	Antioquia	Colombia
14	Cardioangiologisches Centrum Bethanien	Frankfurt		Germany
15	Hospital Santa Cruz	Lisbon		Portugal
16	Hacettepe University	Ankara		Turkey

Sponsors and Collaborators

Montefiore Medical Center
Biosense Webster, Inc.

Investigators

Principal Investigator: Jorge E Romero, MD, Montefiore Medical Center/Albert Einstein College of Medicine
Principal Investigator: Luigi Di Biase, MD, PhD, Montefiore Medical Center/Albert Einstein College of Medicine
Principal Investigator: Andrea Natale, MD, Texas Cardiac Arrhythmia Institute and St. David's Medical Center