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

Not Applicable

Terminated

• Conditions: Atrial Fibrillation
• Interventions: Procedure: Catheter ablation

• Registration Number: NCT04216667
• Lead Sponsor: Montefiore Medical Center

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.

Study Timeline

• Study First Submitted: 2019-12-31
• Study First Submitted QC: 2019-12-31
• Study First Posted: 2020-01-03
• Study Start: 2020-01-16
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-29
• Last Update Posted: 2023-08-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 124

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PVI + PWI	Catheter ablation	Pulmonary vein isolation plus posterior wall isolation will be performed using radiofrequency energy
PVI	Catheter ablation	Pulmonary vein isolation alone will be performed using radiofrequency energy
PVI + PWI + LAAEI	Catheter ablation	Pulmonary vein isolation plus posterior wall isolation plus left atrial appendage electrical isolation will be performed using radiofrequency energy
PVI + PWI + LAAEI + CSI	Catheter ablation	Pulmonary vein isolation plus posterior wall isolation plus left atrial appendage electrical isolation plus coronary sinus isolation will be performed using radiofrequency energy

Primary Outcome Measures

Name	Time	Method
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.
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)

Secondary Outcome Measures

Name	Time	Method
Procedure duration and fluoroscopy time	Day of Procedure	These times will be compared amongst groups
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.
All-cause mortality	12, 24 and 60 months	Death from all causes will be assessed
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.
Number of repeat procedures	12 months	Number of repeat procedures within 12 months after the first ablation procedure
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)
Heart failure analysis	12, 24 and 60 months	Primary outcome will be assessed base on left ventricular ejection fraction (LVEF)
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.
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.
Atrial contractility	6 months	Myocardial strain will be used to assess atrial contractility after catheter ablation
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

Trial Locations

Locations (16)

Cardioangiologisches Centrum Bethanien; 🇩🇪 Frankfurt, Germany

MarinHealth Medical Center; 🇺🇸 Larkspur, California, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Grandview Medical Center; 🇺🇸 Birmingham, Alabama, United States

Miami Cardiac & Vascular Institute; 🇺🇸 Miami, Florida, United States

WakedMed Heart & Vascular; 🇺🇸 Raleigh, North Carolina, United States

Indiana University; 🇺🇸 Bloomington, Indiana, United States

Baylor Heart Clinic; 🇺🇸 Houston, Texas, United States

Texas Cardiac Arrhythmia Institute; 🇺🇸 Austin, Texas, United States

Incor - HCFMUSP; 🇧🇷 Sao Paulo, Brazil

Hacettepe University; 🇹🇷 Ankara, Turkey

Instituto Cardiovascular Adventista; 🇦🇷 Buenos Aires, Argentina

Hospital Santa Cruz; 🇵🇹 Lisbon, Portugal

University CES; 🇨🇴 Medellín, Antioquia, Colombia

University of Colorado; 🇺🇸 Boulder, Colorado, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States