Clinical trial NCT04216667: Posterior Wall And Left Atrial Appendage Empiric Electrical Isolation for Non-Paroxysmal Atrial Fibrillation
Official title: Posterior Wall And Left Atrial Appendage Empiric Electrical Isolation for Non-Paroxysmal Atrial Fibrillation (The PLEA Trial)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Catheter Ablation
Arrhythmia Recurrence
Embolic Stroke
Mortality
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Biosense Webster, Inc.
First posted: 2020-01-03
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 or greater
4. In good general health as evidenced by medical history and diagnosed with symptomatic persistent AF or long-standing persistent AF.

   1. Persistent AF will be defined as a sustained episode lasting \> 7 days and less than 1 year.
   2. Long-standing persistent AF will be defined as a sustained episode lasting more than 1 year and less than 10 years.
   3. 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.
5. 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.
6. Patients undergoing first time procedure for AF.

Exclusion Criteria:

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

Primary outcomes:
measure: Freedom from documented AF/AT/AFL episodes and all-cause mortality after initial procedure
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of peri-procedural and 12-month post procedural complications.
timeFrame: 12, 24 and 60 months
measure: AF/AT/AFL Burden
timeFrame: 12, 24 and 60 months
measure: All-cause mortality
timeFrame: 12, 24 and 60 months
measure: Atrial contractility
timeFrame: 6 months
measure: Heart failure analysis
timeFrame: 12, 24 and 60 months
measure: Cardiovascular hospitalizations
timeFrame: 12, 24 and 60 months
measure: Procedure duration and fluoroscopy time
timeFrame: Day of Procedure
measure: Number of repeat procedures
timeFrame: 12 months
measure: Cost-effectiveness analysis
timeFrame: 12 months
measure: 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
timeFrame: 24 and 60 months
measure: Freedom from documented AF/AT/AFL episodes (>30 seconds) and all-cause mortality within 12 months after redo ablation procedure.
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Center
state: Alabama
city: Larkspur
country: United States
facility: MarinHealth Medical Center
state: California
city: Boulder
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: Miami Cardiac & Vascular Institute
state: Florida
city: Bloomington
country: United States
facility: Indiana University
state: Indiana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Raleigh
country: United States
facility: WakedMed Heart & Vascular
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Institute
state: Texas
city: Houston
country: United States
facility: Baylor Heart Clinic
state: Texas
city: Buenos Aires
country: Argentina
facility: Instituto Cardiovascular Adventista
city: Sao Paulo
country: Brazil
facility: Incor - HCFMUSP
city: Medellín
country: Colombia
facility: University CES
state: Antioquia
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum Bethanien
city: Lisbon
country: Portugal
facility: Hospital Santa Cruz
city: Ankara
country: Turkey
facility: Hacettepe University
Study officials:
affiliation: Montefiore Medical Center/Albert Einstein College of Medicine
name: Jorge E Romero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center/Albert Einstein College of Medicine
name: Luigi Di Biase, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Cardiac Arrhythmia Institute and St. David's Medical Center
name: Andrea Natale, MD
role: PRINCIPAL_INVESTIGATOR
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