Clinical trial NCT07021313: Deliver mOre aPplications for More Durable Pulmonary Vein IsOlation
Official title: Deliver mOre aPplications for More Durable Pulmonary Vein IsOlation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Pulsed Field Ablation
Atrial Fibrillation
Lead sponsor: R&D Cardiologie
Sponsor class: OTHER
First posted: 2025-06-13
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in a 1:1 fashion with a block size of 4 to the study arm or the usual care (control) arm.
Primary purpose: TREATMENT

Brief summary: Pulmonary vein isolation (PVI) by catheter ablation (CA) has become a widely accepted interventional treatment for patients with symptomatic atrial fibrillation (AF) despite anti-arrhythmic drugs (AAD). Classic thermal ablation modalities use radiofrequency energy or cryo-energy to create cardiac tissue lesions. Irreversible electroporation (IRE) using pulsed field energy (PFA) is a novel technology for cardiac tissue ablation. Initial studies have shown favorable outcome data in patients with AF treated by performing PVI using PFA. However, the freedom of AF has not yet proven superior to existing thermal ablation methods and appears similarly associated with suboptimal lesion durability, leading to electrical reconnection. The purpose of this study is to determine if freedom of atrial fibrillation may be improved by delivering more and better targeted pulsed field ablations.

Detailed description: Pulmonary vein isolation (PVI) by catheter ablation (CA) has become a widely accepted interventional treatment for patients with symptomatic atrial fibrillation (AF) despite anti-arrhythmic drugs (AAD). Classic thermal ablation modalities use radiofrequency energy or cryo-energy to create cardiac tissue lesions. Irreversible electroporation (IRE) using pulsed field energy (PFA) is a novel technology for cardiac tissue ablation. Initial studies have shown favorable outcome data in patients with AF treated by performing PVI using PFA. However, the freedom of AF has not yet proven superior to existing thermal ablation methods and appears similarly associated with suboptimal lesion durability, leading to electrical reconnection. The purpose of this study is to determine if freedom of atrial fibrillation may be improved by delivering more and better targeted pulsed field ablations. Patients will undergo the standard catheter ablation procedure in accordance with good clinical practice, performing pulmonary vein islolation (PVI) with the FARAPULSE cardiac ablation system. In the control group PVI will be performed with 4 basket- and 4 flower-shaped applications of the catheter, while in the study group 2 olive-, 4 basket-, and 6 flower shaped applications will be delivered at each vein. All other procedural steps will be the same between groups. Patients will be randomized in a 1:1 fashion with a block size of 4 to the study arm or the usual care (control) arm. The primary study parameter for efficacy is the freedom of atrial arrhythmias after the 2-month blanking period up to 12 months after the procedure. The secondary study outcomes include the extent and position of pulmonary vein reconnection observed during redo procedures that are performed due to arrhythmia recurrence, which constitutes a study endpoint. Furthermore, the study also evaluates arrhythmia burden after the procedure in centers that routinely use photoplethysmographic remote monitoring as standard care for all their ablation patients.

Eligibility criteria: Inclusion Criteria:

* Be scheduled for PVI with the use of the FARAPULSE catheter ablation system AND
* Have paroxysmal atrial fibrillation (PAF) documented in the last 6 months prior to enrolment OR
* Had persistent atrial fibrillation but maintained in SR or converted to paroxysmal by antiarrhythmic drugs with no more than 1 cardioversion beyond 7 days in the past

Exclusion Criteria:

* Cerebrovascular accident (CVA) in the last 6 months
* More than moderate valvular disease that would require intervention
* Cardiac catheter/surgical intervention in the last 3 months or scheduled
* Atrial septal defect (ASD)/ patent foramen ovale (PFO) closure in the past
* Left atrial appendage (LAA) closure in the past
* Mechanical mitral valve
* Non-adherence to oral anticoagulation in the 3 weeks prior to ablation
* Renal disease with known eGFR\<45 ml
* Left atrial volume index (LAVI) \>50 ml/m2 or left atrial diameter (LAD) \>50 mm
* Known contra-indication for catheter ablation
* Known contra-indication for deep sedation or general anesthesia
* Known pregnancy

Primary outcomes:
measure: Freedom of atrial fibrillation after a 2-month blanking period up to 12 months post procedure.
timeFrame: Baseline, month 3, month 6, month 12.
Secondary outcomes:
measure: Procedural-up-to-30 days and 30 days up-to 12 months safety of increasing PFA application numbers
timeFrame: From procedure to 12-month follow-up
measure: Quality of life differences between groups
timeFrame: Baseline, month 3, month 6, month 12.
measure: The potential for hemolysis in relation to application number
timeFrame: Post procedure every 24 hours, up to 5 days post procedure for each individual patient
measure: The durability of pulmonary vein isolation in case of a redo procedure
timeFrame: Month 3, month 6, month 12.
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
Study officials:
affiliation: St. Antonius Hospital
name: Lucas VA Boersma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boersma L, Andrade JG, Betts T, Duytschaever M, Purerfellner H, Santoro F, Tzeis S, Verma A. Progress in atrial fibrillation ablation during 25 years of Europace journal. Europace. 2023 Aug 2;25(9):euad244. doi: 10.1093/europace/euad244.
citation: Kawamura I, Neuzil P, Shivamurthy P, Kuroki K, Lam J, Musikantow D, Chu E, Turagam MK, Minami K, Funasako M, Petru J, Choudry S, Miller MA, Langan MN, Whang W, Dukkipati SR, Koruth JS, Reddy VY. How does the level of pulmonary venous isolation compare between pulsed field ablation and thermal energy ablation (radiofrequency, cryo, or laser)? Europace. 2021 Nov 8;23(11):1757-1766. doi: 10.1093/europace/euab150.
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, Cosedis Nielsen J, Curtis AB, Davies DW, Day JD, d'Avila A, Natasja de Groot NMS, 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; Document Reviewers:. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2018 Jan 1;20(1):e1-e160. doi: 10.1093/europace/eux274. No abstract available.
citation: Koruth J, Verma A, Kawamura I, Reinders D, Andrade JG, Deyell MW, Mehta N, Reddy VY. PV Isolation Using a Spherical Array PFA Catheter: Preclinical Assessment and Comparison to Radiofrequency Ablation. JACC Clin Electrophysiol. 2023 May;9(5):652-666. doi: 10.1016/j.jacep.2023.01.022. Epub 2023 Feb 3.
citation: Futing A, Reinsch N, Howel D, Brokkaar L, Rahe G, Neven K. First experience with pulsed field ablation as routine treatment for paroxysmal atrial fibrillation. Europace. 2022 Jul 21;24(7):1084-1092. doi: 10.1093/europace/euac041.
citation: Verma A, Asivatham SJ, Deneke T, Castellvi Q, Neal RE 2nd. Primer on Pulsed Electrical Field Ablation: Understanding the Benefits and Limitations. Circ Arrhythm Electrophysiol. 2021 Sep;14(9):e010086. doi: 10.1161/CIRCEP.121.010086. Epub 2021 Sep 20.
citation: Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, Dukkipati SR, Jais P. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019 Jul 23;74(3):315-326. doi: 10.1016/j.jacc.2019.04.021. Epub 2019 May 11.
citation: Hartl S, Reinsch N, Futing A, Neven K. Pearls and Pitfalls of Pulsed Field Ablation. Korean Circ J. 2023 May;53(5):273-293. doi: 10.4070/kcj.2023.0023.
citation: Reddy VY, Dukkipati SR, Neuzil P, Anic A, Petru J, Funasako M, Cochet H, Minami K, Breskovic T, Sikiric I, Sediva L, Chovanec M, Koruth J, Jais P. Pulsed Field Ablation of Paroxysmal Atrial Fibrillation: 1-Year Outcomes of IMPULSE, PEFCAT, and PEFCAT II. JACC Clin Electrophysiol. 2021 May;7(5):614-627. doi: 10.1016/j.jacep.2021.02.014. Epub 2021 Apr 28.
citation: Reddy VY, Gerstenfeld EP, Natale A, Whang W, Cuoco FA, Patel C, Mountantonakis SE, Gibson DN, Harding JD, Ellis CR, Ellenbogen KA, DeLurgio DB, Osorio J, Achyutha AB, Schneider CW, Mugglin AS, Albrecht EM, Stein KM, Lehmann JW, Mansour M; ADVENT Investigators. Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2023 Nov 2;389(18):1660-1671. doi: 10.1056/NEJMoa2307291. Epub 2023 Aug 27.
citation: Schmidt B, Bordignon S, Neven K, Reichlin T, Blaauw Y, Hansen J, Adelino R, Ouss A, Futing A, Roten L, Mulder BA, Ruwald MH, Mene R, van der Voort P, Reinsch N, Kueffer T, Boveda S, Albrecht EM, Schneider CW, Chun KRJ. EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry. Europace. 2023 Jul 4;25(7):euad185. doi: 10.1093/europace/euad185.
citation: Verma A, Haines DE, Boersma LV, Sood N, Natale A, Marchlinski FE, Calkins H, Sanders P, Packer DL, Kuck KH, Hindricks G, Onal B, Cerkvenik J, Tada H, DeLurgio DB; PULSED AF Investigators. Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial. Circulation. 2023 May 9;147(19):1422-1432. doi: 10.1161/CIRCULATIONAHA.123.063988. Epub 2023 Mar 6.
citation: Tohoku S, Chun KRJ, Bordignon S, Chen S, Schaack D, Urbanek L, Ebrahimi R, Hirokami J, Bologna F, Schmidt B. Findings from repeat ablation using high-density mapping after pulmonary vein isolation with pulsed field ablation. Europace. 2023 Feb 16;25(2):433-440. doi: 10.1093/europace/euac211.
citation: Nakatani Y, Sridi-Cheniti S, Cheniti G, Ramirez FD, Goujeau C, Andre C, Nakashima T, Eggert C, Schneider C, Viswanathan R, Krisai P, Takagi T, Kamakura T, Vlachos K, Derval N, Duchateau J, Pambrun T, Chauvel R, Reddy VY, Montaudon M, Laurent F, Sacher F, Hocini M, Haissaguerre M, Jais P, Cochet H. Pulsed field ablation prevents chronic atrial fibrotic changes and restrictive mechanics after catheter ablation for atrial fibrillation. Europace. 2021 Nov 8;23(11):1767-1776. doi: 10.1093/europace/euab155.
citation: Cochet H, Nakatani Y, Sridi-Cheniti S, Cheniti G, Ramirez FD, Nakashima T, Eggert C, Schneider C, Viswanathan R, Derval N, Duchateau J, Pambrun T, Chauvel R, Reddy VY, Montaudon M, Laurent F, Sacher F, Hocini M, Haissaguerre M, Jais P. Pulsed field ablation selectively spares the oesophagus during pulmonary vein isolation for atrial fibrillation. Europace. 2021 Sep 8;23(9):1391-1399. doi: 10.1093/europace/euab090.
citation: Musikantow DR, Neuzil P, Petru J, Koruth JS, Kralovec S, Miller MA, Funasako M, Chovanec M, Turagam MK, Whang W, Sediva L, Dukkipati SR, Reddy VY. Pulsed Field Ablation to Treat Atrial Fibrillation: Autonomic Nervous System Effects. JACC Clin Electrophysiol. 2023 Apr;9(4):481-493. doi: 10.1016/j.jacep.2022.10.028. Epub 2022 Nov 30.
citation: Reddy VY, Petru J, Funasako M, Kopriva K, Hala P, Chovanec M, Janotka M, Kralovec S, Neuzil P. Coronary Arterial Spasm During Pulsed Field Ablation to Treat Atrial Fibrillation. Circulation. 2022 Dec 13;146(24):1808-1819. doi: 10.1161/CIRCULATIONAHA.122.061497. Epub 2022 Sep 22.
citation: Bohnen M, Weber R, Minners J, Jadidi A, Eichenlaub M, Neumann FJ, Arentz T, Lehrmann H. Characterization of circumferential antral pulmonary vein isolation areas resulting from pulsed-field catheter ablation. Europace. 2023 Feb 8;25(1):65-73. doi: 10.1093/europace/euac111.
citation: Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998 Sep 3;339(10):659-66. doi: 10.1056/NEJM199809033391003.
citation: Patel C, Gerstenfeld EP, Gupta SK, Winterfield J, Woods C, Natale A, Schneider CW, Achyutha AB, Holland SK, Richards E, Albrecht EM, Lehmann JW, Mansour M, Reddy VY. Comparison of cerebral safety after atrial fibrillation using pulsed field and thermal ablation: Results of the neurological assessment subgroup in the ADVENT trial. Heart Rhythm. 2024 Nov;21(11):2103-2109. doi: 10.1016/j.hrthm.2024.05.048. Epub 2024 May 31.
citation: Mansour M, Gerstenfeld EP, Patel C, Natale A, Whang W, Cuoco FA, Mountantonakis SE, Gibson DN, Harding JD, Holland SK, Achyutha AB, Schneider CW, Mugglin AS, Albrecht EM, Stein KM, Lehmann JW, Reddy VY. Pulmonary vein narrowing after pulsed field versus thermal ablation. Europace. 2024 Feb 1;26(2):euae038. doi: 10.1093/europace/euae038.
citation: Reddy VY, Anic A, Koruth J, Petru J, Funasako M, Minami K, Breskovic T, Sikiric I, Dukkipati SR, Kawamura I, Neuzil P. Pulsed Field Ablation in Patients With Persistent Atrial Fibrillation. J Am Coll Cardiol. 2020 Sep 1;76(9):1068-1080. doi: 10.1016/j.jacc.2020.07.007.
citation: du Pre BC, van Driel VJ, van Wessel H, Loh P, Doevendans PA, Goldschmeding R, Wittkampf FH, Vink A. Minimal coronary artery damage by myocardial electroporation ablation. Europace. 2013 Jan;15(1):144-9. doi: 10.1093/europace/eus171. Epub 2012 May 31.
citation: Moshkovits Y, Grynberg D, Heller E, Maizels L, Maor E. Differential effect of high-frequency electroporation on myocardium vs. non-myocardial tissues. Europace. 2023 Feb 16;25(2):748-755. doi: 10.1093/europace/euac191.
citation: Popa MA, Venier S, Mene R, Della Rocca DG, Sacher F, Derval N, Hocini M, Dulucq S, Caluori G, Combes S, Albenque JP, Saitta F, Haller B, Chierchia GB, de Asmundis C, Defaye P, Boveda S, Jais P. Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis. Circ Arrhythm Electrophysiol. 2024 Oct;17(10):e012732. doi: 10.1161/CIRCEP.124.012732. Epub 2024 Aug 30.