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

Atrial Fibrillation Clinical Trial

— PLEA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04216667
• Other study ID #: 2019-10714
• Status: Terminated
• Phase: N/A
• Start date: January 16, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2023
• Source: Montefiore Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 124
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Catheter ablation
Catheter ablation

Locations

Country	Name	City	State
Argentina	Instituto Cardiovascular Adventista	Buenos Aires
Brazil	Incor - HCFMUSP	Sao Paulo
Colombia	University CES	Medellín	Antioquia
Germany	Cardioangiologisches Centrum Bethanien	Frankfurt
Portugal	Hospital Santa Cruz	Lisbon
Turkey	Hacettepe University	Ankara
United States	Texas Cardiac Arrhythmia Institute	Austin	Texas
United States	Grandview Medical Center	Birmingham	Alabama
United States	Indiana University	Bloomington	Indiana
United States	University of Colorado	Boulder	Colorado
United States	Montefiore Medical Center	Bronx	New York
United States	Baylor Heart Clinic	Houston	Texas
United States	MarinHealth Medical Center	Larkspur	California
United States	Miami Cardiac & Vascular Institute	Miami	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	WakedMed Heart & Vascular	Raleigh	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Montefiore Medical Center	Biosense Webster, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Colombia,  Germany,  Portugal,  Turkey, 

References & Publications (22)

Allessie MA, de Groot NM, Houben RP, Schotten U, Boersma E, Smeets JL, Crijns HJ. Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation. Circ Arrhythm Electrophysiol. 2010 Dec;3(6):606-15. doi: 10.1161/CIRCEP.109.910125. Epub 2010 Aug 18. — View Citation

Aryana A, Baker JH, Espinosa Ginic MA, Pujara DK, Bowers MR, O'Neill PG, Ellenbogen KA, Di Biase L, d'Avila A, Natale A. Posterior wall isolation using the cryoballoon in conjunction with pulmonary vein ablation is superior to pulmonary vein isolation alone in patients with persistent atrial fibrillation: A multicenter experience. Heart Rhythm. 2018 Aug;15(8):1121-1129. doi: 10.1016/j.hrthm.2018.05.014. — View Citation

Bai R, Di Biase L, Mohanty P, Trivedi C, Dello Russo A, Themistoclakis S, Casella M, Santarelli P, Fassini G, Santangeli P, Mohanty S, Rossillo A, Pelargonio G, Horton R, Sanchez J, Gallinghouse J, Burkhardt JD, Ma CS, Tondo C, Natale A. Proven isolation of the pulmonary vein antrum with or without left atrial posterior wall isolation in patients with persistent atrial fibrillation. Heart Rhythm. 2016 Jan;13(1):132-40. doi: 10.1016/j.hrthm.2015.08.019. Epub 2015 Aug 13. — View Citation

Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017 Mar 7;135(10):e146-e603. doi: 10.1161/CIR.0000000000000485. Epub 2017 Jan 25. No abstract available. Erratum In: Circulation. 2017 Mar 7;135(10 ):e646. Circulation. 2017 Sep 5;136(10 ):e196. — View Citation

Brooks AG, Stiles MK, Laborderie J, Lau DH, Kuklik P, Shipp NJ, Hsu LF, Sanders P. Outcomes of long-standing persistent atrial fibrillation ablation: a systematic review. Heart Rhythm. 2010 Jun;7(6):835-46. doi: 10.1016/j.hrthm.2010.01.017. Epub 2010 Jan 22. — View Citation

Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Nielsen JC, Curtis AB, Davies DW, Day JD, d'Avila A, de Groot NMSN, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. Europace. 2018 Jan 1;20(1):157-208. doi: 10.1093/europace/eux275. No abstract available. — View Citation

Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH Jr, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014 Feb 25;129(8):837-47. doi: 10.1161/CIRCULATIONAHA.113.005119. Epub 2013 Dec 17. — View Citation

Di Biase L, Burkhardt JD, Mohanty P, Mohanty S, Sanchez JE, Trivedi C, Gunes M, Gokoglan Y, Gianni C, Horton RP, Themistoclakis S, Gallinghouse GJ, Bailey S, Zagrodzky JD, Hongo RH, Beheiry S, Santangeli P, Casella M, Dello Russo A, Al-Ahmad A, Hranitzky P, Lakkireddy D, Tondo C, Natale A. Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation: BELIEF Trial. J Am Coll Cardiol. 2016 Nov 1;68(18):1929-1940. doi: 10.1016/j.jacc.2016.07.770. — View Citation

Di Biase L, Burkhardt JD, Mohanty P, Sanchez J, Mohanty S, Horton R, Gallinghouse GJ, Bailey SM, Zagrodzky JD, Santangeli P, Hao S, Hongo R, Beheiry S, Themistoclakis S, Bonso A, Rossillo A, Corrado A, Raviele A, Al-Ahmad A, Wang P, Cummings JE, Schweikert RA, Pelargonio G, Dello Russo A, Casella M, Santarelli P, Lewis WR, Natale A. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation. 2010 Jul 13;122(2):109-18. doi: 10.1161/CIRCULATIONAHA.109.928903. Epub 2010 Jul 6. — View Citation

Heeger CH, Rillig A, Geisler D, Wohlmuth P, Fink T, Mathew S, Tilz RR, Reissmann B, Lemes C, Maurer T, Santoro F, Inaba O, Sohns C, Huang Y, Alessandrini H, Dotz I, Schluter M, Metzner A, Kuck KH, Ouyang F. Left Atrial Appendage Isolation in Patients Not Responding to Pulmonary Vein Isolation. Circulation. 2019 Jan 29;139(5):712-715. doi: 10.1161/CIRCULATIONAHA.118.037451. No abstract available. — View Citation

Hocini M, Shah AJ, Nault I, Sanders P, Wright M, Narayan SM, Takahashi Y, Jais P, Matsuo S, Knecht S, Sacher F, Lim KT, Clementy J, Haissaguerre M. Localized reentry within the left atrial appendage: arrhythmogenic role in patients undergoing ablation of persistent atrial fibrillation. Heart Rhythm. 2011 Dec;8(12):1853-61. doi: 10.1016/j.hrthm.2011.07.013. Epub 2011 Jul 12. — View Citation

Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4. — View Citation

Lakkireddy D, Sridhar Mahankali A, Kanmanthareddy A, Lee R, Badhwar N, Bartus K, Atkins D, Bommana S, Cheng J, Rasekh A, Di Biase L, Natale A, Nath J, Ferrell R, Earnest M, Reddy YM. Left Atrial Appendage Ligation and Ablation for Persistent Atrial Fibrillation: The LAALA-AF Registry. JACC Clin Electrophysiol. 2015 Jun;1(3):153-160. doi: 10.1016/j.jacep.2015.04.006. Epub 2015 Apr 30. — View Citation

Lim HS, Hocini M, Dubois R, Denis A, Derval N, Zellerhoff S, Yamashita S, Berte B, Mahida S, Komatsu Y, Daly M, Jesel L, Pomier C, Meillet V, Amraoui S, Shah AJ, Cochet H, Sacher F, Jais P, Haissaguerre M. Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation. J Am Coll Cardiol. 2017 Mar 14;69(10):1257-1269. doi: 10.1016/j.jacc.2017.01.014. — View Citation

Lim TW, Koay CH, See VA, McCall R, Chik W, Zecchin R, Byth K, Seow SC, Thomas L, Ross DL, Thomas SP. Single-ring posterior left atrial (box) isolation results in a different mode of recurrence compared with wide antral pulmonary vein isolation on long-term follow-up: longer atrial fibrillation-free survival time but similar survival time free of any atrial arrhythmia. Circ Arrhythm Electrophysiol. 2012 Oct;5(5):968-77. doi: 10.1161/CIRCEP.111.970293. Epub 2012 Sep 12. — View Citation

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Panikker S, Jarman JW, Virmani R, Kutys R, Haldar S, Lim E, Butcher C, Khan H, Mantziari L, Nicol E, Foran JP, Markides V, Wong T. Left Atrial Appendage Electrical Isolation and Concomitant Device Occlusion to Treat Persistent Atrial Fibrillation: A First-in-Human Safety, Feasibility, and Efficacy Study. Circ Arrhythm Electrophysiol. 2016 Jul;9(7):e003710. doi: 10.1161/CIRCEP.115.003710. — View Citation

Romero J, Michaud GF, Avendano R, Briceno DF, Kumar S, Carlos Diaz J, Mohanty S, Trivedi C, Gianni C, Della Rocca D, Proietti R, Perrotta L, Bordignon S, Chun JKR, Schmidt B, Garcia M, Natale A, Di Biase L. Benefit of left atrial appendage electrical isolation for persistent and long-standing persistent atrial fibrillation: a systematic review and meta-analysis. Europace. 2018 Aug 1;20(8):1268-1278. doi: 10.1093/europace/eux372. — View Citation

Romero J, Natale A, Di Biase L. Left atrial appendage empirical electrical isolation for persistent atrial fibrillation: time for a change in practice. Europace. 2017 May 1;19(5):699-702. doi: 10.1093/europace/eux050. No abstract available. — View Citation

Tamborero D, Mont L, Berruezo A, Matiello M, Benito B, Sitges M, Vidal B, de Caralt TM, Perea RJ, Vatasescu R, Brugada J. Left atrial posterior wall isolation does not improve the outcome of circumferential pulmonary vein ablation for atrial fibrillation: a prospective randomized study. Circ Arrhythm Electrophysiol. 2009 Feb;2(1):35-40. doi: 10.1161/CIRCEP.108.797944. Epub 2008 Dec 3. — View Citation

Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P; STAR AF II Investigators. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015 May 7;372(19):1812-22. doi: 10.1056/NEJMoa1408288. — View Citation

Yorgun H, Canpolat U, Kocyigit D, Coteli C, Evranos B, Aytemir K. Left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation: one-year clinical outcome after cryoballoon-based ablation. Europace. 2017 May 1;19(5):758-768. doi: 10.1093/europace/eux005. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from documented AF/AT/AFL episodes and all-cause mortality after initial procedure	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)	12 months
Primary	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.	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.	12 months
Secondary	Incidence of peri-procedural and 12-month post procedural complications.	These complications include: ischemic stroke, pulmonary veins (PVs) stenosis, cardiac perforation, esophageal injury, phrenic nerve paralysis, rehospitalization, and death.	12, 24 and 60 months
Secondary	AF/AT/AFL Burden	Atrial fibrillation (AF), atrial tachycardia (AT) and/or atrial flutter (AFL) burden at 12 months after single and redo procedures	12, 24 and 60 months
Secondary	All-cause mortality	Death from all causes will be assessed	12, 24 and 60 months
Secondary	Atrial contractility	Myocardial strain will be used to assess atrial contractility after catheter ablation	6 months
Secondary	Heart failure analysis	Primary outcome will be assessed base on left ventricular ejection fraction (LVEF)	12, 24 and 60 months
Secondary	Cardiovascular hospitalizations	Cardiovascular hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.	12, 24 and 60 months
Secondary	Procedure duration and fluoroscopy time	These times will be compared amongst groups	Day of Procedure
Secondary	Number of repeat procedures	Number of repeat procedures within 12 months after the first ablation procedure	12 months
Secondary	Cost-effectiveness analysis	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.	12 months
Secondary	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	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)	24 and 60 months
Secondary	Freedom from documented AF/AT/AFL episodes (>30 seconds) and all-cause mortality within 12 months after redo ablation procedure.	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.	12 months