Atrial Fibrillation
Conditions
Keywords
Catheter Ablation, Arrhythmia Recurrence, Embolic Stroke, Mortality
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.
Interventions
PROCEDURECatheter ablation
Catheter ablation
Sponsors
Biosense Webster, Inc.
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Procedure duration and fluoroscopy time | Day of Procedure | These times will be compared amongst groups |
| 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 |
Countries
Argentina, Brazil, Colombia, Germany, Portugal, Turkey (Türkiye), United States
Outcome results
None listed