Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure

NCT ID: NCT05264831

Last Updated: 2024-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

450 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-20

Study Completion Date

2027-10-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study aims at assessing whether electric cardioversion can act as a discriminant factor between patients requiring Pulmonary Vein Isolation (PVI) procedure alone or PVI procedure combined with substrate modulation.

All included patients will undergo an electric cardioversion, then:

* Patients with electric cardioversion success will be treated as per Standard of Care and according to ESC recommendations (2020). A prospective registry will be implemented for these patients.
* Patients with electric cardioversion failure will be randomized in the study between 2 ablative procedures:

* PVI procedure alone
* PVI procedure combined with substrate modulation

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Atrial fibrillation (AF) is the most common heart rhythm disorder. It is the result of uncoordinated action of the atrial myocardial cells, causing rapid and irregular contraction of the heart's atria.

The AF prevalence in adults is currently estimated to be between 2% and 4% and is expected to increase by a factor of 2.3 in the next few years, due to the increased longevity of the general population and the increased search for undiagnosed AF. Increased age is an important risk factor for AF, but other increased comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic renal failure, obesity, and obstructive sleep apnoea syndrome, are also important; modifiable risk factors contribute strongly to the development and progression of AF (ESC Guideline, 2020).

The European Society of Cardiology (ESC) recommended pulmonary vein isolation (PVI) (Class IA) as first-line ablative strategy for persistent AF (Class IA) (ESC Guideline, 2020). However, PVI alone is only effective in treating about 40% to 60% of patients with persistent AF in the general population (unselected). If we apply this strategy to all patients (PVI alone), we accept to re-do ablative procedure in up to 60% of patients.

The second feasible strategy is to treat patients with persistent AF by PVI combined with substrate modulation (ESC Class IIb). This strategy, when done well, by creating irreversible lesions (Marshall-PLAN) can effectively treat 70% to 80% of AF patients. But this implies that the investigator will be doing unnecessary substrate modulation in up to 40% of patients, which can lead to increased risks associated with the ablative procedure, longer procedure times, multiple lesions, etc… In addition, incorrect or incomplete substrate modulation is pro-arrhythmic and leads to recurrences in the form of left atrial flutters, tolerance of which, is generally poor.

Both ablative strategies have been widely validated in large numbers of published studies.

The problem is to know when and for which patients to apply one or the other of the two strategies. Electric cardioversion could help in selecting the most appropriate strategy.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Persistent Atrial Fibrillation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study procedure is the electric cardioversion as a discriminant factor between patients requiring PVI procedure alone or PVI procedure combined with substrate modulation. This electric cardioversion will be performed in all included patients up to 6 weeks before the ablative procedure.

On the day of the ablative procedure:

* If the patient presents with a Sinus Rhythm (= successful electric cardioversion, approximately 70% of patients) the patient will be treated as per SoC in accordance with ESC recommendations. It is recommended to perform PVI procedure alone in these patients. A prospective registry for these patients will be established for this study.
* If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to the 2 strategies:
* Group 1: PVI procedure alone in accordance with ESC recommendations
* Group 2: PVI procedure associated with substrate modulation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

N/A, open label.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

PVI procedure alone

If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to :

\- Group 1: PVI procedure alone in accordance with ESC recommendations

Group Type ACTIVE_COMPARATOR

Pulmonary Vein Isolation (PVI) alone

Intervention Type PROCEDURE

PVI procedures correspond to point-by-point 50W AI-guided RF applications (400 posterior LA wall, and 550 elsewhere). The PVI will be validated by the absence of any activity recorded inside the PV encirclement by a multipolar catheter (either a Lasso catheter or a Pentaray catheter) (entrance block) and by the non-capture of the LA despite pacing maneuvers from inside the encirclement (exit block). The bidirectional block will be validated again after a 15-minutes waiting period.

PVI procedure combined with substrate modulation

If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to :

\- Group 2: PVI procedure associated with substrate modulation

Group Type EXPERIMENTAL

PVI procedure associated with substrate modulation

Intervention Type PROCEDURE

PVI procedure associated with substrate modulation

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pulmonary Vein Isolation (PVI) alone

PVI procedures correspond to point-by-point 50W AI-guided RF applications (400 posterior LA wall, and 550 elsewhere). The PVI will be validated by the absence of any activity recorded inside the PV encirclement by a multipolar catheter (either a Lasso catheter or a Pentaray catheter) (entrance block) and by the non-capture of the LA despite pacing maneuvers from inside the encirclement (exit block). The bidirectional block will be validated again after a 15-minutes waiting period.

Intervention Type PROCEDURE

PVI procedure associated with substrate modulation

PVI procedure associated with substrate modulation

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Criteria to be validated for patients included before performing electric cardioversion:

1\) Persistent AF (continuous for at least 7 days without interruption according to information transmitted by the cardiologist and the patient), symptomatic and resistant to at leat one anti-arrhythmic drug treatment including amiodarone;

Criteria to be validated for patients included after performing electric cardioversion :

1. Patient treated by electric cardioversion for persistent AF, symptomatic and resistant to anti-arrhythmic treatment including amiodarone and whom ablative procedure is planned in the following 4-6 weeks after electric cardioversion

Criteria to be validated for all patients included:
2. Life expectancy \> 5 years;
3. Female or male between 18 and 80 years of age at the electric cardioversion time
4. Affiliation to a health insurance system;
5. Patient informed of the study and having signed informed consent

Criteria to be validated prior to randomization on the day of ablation (these patients may be randomized):
6. Patient with failed electric cardioversion i.e. in AF, confirmed by ECG.

Exclusion Criteria

Criteria to be validated before or after performing electric cardioversion (the study cannot be proposed to patients corresponding to these criteria):

1. Current hyperthyroidism;
2. Pregnant or breastfeeding woman;
3. Patient with a Body Mass Index (BMI) greater than 35;
4. Patient with severe Chronic Obstructive Pulmonary Disease (COPD);
5. Patient with hypertrophic heart disease;
6. Patient with a mechanical or biological mitral valve;
7. Contraindications to anticoagulants;
8. Transient Ischemic Attack (TIA) /stroke less than 6 months old;
9. Psychiatric illness affecting follow-up;
10. Left Ventricular Ejection Fraction (LVEF) \< 40% ;
11. Uncontrolled ischaemic heart disease (angina, myocardial ischaemia)
12. Patients under legal protection
13. Cardiac surgery on left atrium
14. Inflammatory status in progress (cancer, rheumatoid arthritis, PPRZ, acute or chronic periodontitis, Crohn's disease, RCUH)
15. Pulmonary embolism or phlebitis less than 6 months old
16. Prior atrial fibrillation ablation
17. Active cancer

Criteria to be validated before randomization, on the day of ablation (these patients cannot be randomized):
18. Patient in sinus rhythm 4-6 weeks after electric cardioversion: these patients are included in the study registry.
19. Patient with complete absence of sinus rhythm (less than 10 seconds) after 3 electric cardioversion attempts: these patients will discontinue from the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Elsan

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Augustin Bortone, MD

Role: STUDY_DIRECTOR

Elsan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Infirmerie Protestante

Caluire-et-Cuire, , France

Site Status RECRUITING

CH Libourne

Libourne, , France

Site Status NOT_YET_RECRUITING

CHU Lille

Lille, , France

Site Status ACTIVE_NOT_RECRUITING

Hopital ST Phillbert

Lomme, , France

Site Status NOT_YET_RECRUITING

CMC Ambroise Paré Hartmann

Neuilly-sur-Seine, , France

Site Status NOT_YET_RECRUITING

Hôpital Privé Les Franciscaines

Nîmes, , France

Site Status RECRUITING

Hôpital Européen Georges Pompidou Service de cardiologie - Unité rythmologie

Paris, , France

Site Status RECRUITING

Clinique St Pierre Cardiologie

Perpignan, , France

Site Status RECRUITING

CHU Rennes

Rennes, , France

Site Status RECRUITING

CCN

Saint-Denis, , France

Site Status NOT_YET_RECRUITING

Clinique Rhéna

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Clinique Pasteur Service de cardiologie/rythmologie

Toulouse, , France

Site Status RECRUITING

Chu Nancy

Vandœuvre-lès-Nancy, , France

Site Status NOT_YET_RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Agustín Bortone, MD

Role: CONTACT

04 66 26 63 75 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Cyril Durand, MD

Role: primary

Rim EL BOUAZZAOUI, MD

Role: primary

Yves Guyomar, MD

Role: primary

Alexandre Zhao, MD

Role: primary

Agustín Bortone, MD

Role: primary

Emilie Varlet, MD

Role: primary

Philippe Lagrange, MD

Role: primary

Raphael Martins, MD

Role: primary

Antoine Lepillier, MD

Role: primary

Matjieu Schaaf, MD

Role: primary

Jean-Paul Albenque, MD

Role: primary

Jean-Marc SELLAL, MD

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL. Corrigendum to: 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Oct 21;42(40):4194. doi: 10.1093/eurheartj/ehab648. No abstract available.

Reference Type BACKGROUND
PMID: 34520521 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25946280 (View on PubMed)

Sanders P, Hocini M, Jais P, Sacher F, Hsu LF, Takahashi Y, Rotter M, Rostock T, Nalliah CJ, Clementy J, Haissaguerre M. Complete isolation of the pulmonary veins and posterior left atrium in chronic atrial fibrillation. Long-term clinical outcome. Eur Heart J. 2007 Aug;28(15):1862-71. doi: 10.1093/eurheartj/ehl548.

Reference Type BACKGROUND
PMID: 17341503 (View on PubMed)

Knecht S, Hocini M, Wright M, Lellouche N, O'Neill MD, Matsuo S, Nault I, Chauhan VS, Makati KJ, Bevilacqua M, Lim KT, Sacher F, Deplagne A, Derval N, Bordachar P, Jais P, Clementy J, Haissaguerre M. Left atrial linear lesions are required for successful treatment of persistent atrial fibrillation. Eur Heart J. 2008 Oct;29(19):2359-66. doi: 10.1093/eurheartj/ehn302. Epub 2008 Jul 8.

Reference Type BACKGROUND
PMID: 18614522 (View on PubMed)

Valderrabano M, Peterson LE, Bunge R, Prystash M, Dave AS, Nagueh S, Kleiman NS. Vein of Marshall ethanol infusion for persistent atrial fibrillation: VENUS and MARS clinical trial design. Am Heart J. 2019 Sep;215:52-61. doi: 10.1016/j.ahj.2019.04.022. Epub 2019 May 11.

Reference Type BACKGROUND
PMID: 31279972 (View on PubMed)

Kim DT, Lai AC, Hwang C, Fan LT, Karagueuzian HS, Chen PS, Fishbein MC. The ligament of Marshall: a structural analysis in human hearts with implications for atrial arrhythmias. J Am Coll Cardiol. 2000 Oct;36(4):1324-7. doi: 10.1016/s0735-1097(00)00819-6.

Reference Type BACKGROUND
PMID: 11028490 (View on PubMed)

Valderrabano M, Chen HR, Sidhu J, Rao L, Ling Y, Khoury DS. Retrograde ethanol infusion in the vein of Marshall: regional left atrial ablation, vagal denervation and feasibility in humans. Circ Arrhythm Electrophysiol. 2009 Feb;2(1):50-6. doi: 10.1161/CIRCEP.108.818427.

Reference Type BACKGROUND
PMID: 19756206 (View on PubMed)

Dave AS, Baez-Escudero JL, Sasaridis C, Hong TE, Rami T, Valderrabano M. Role of the vein of Marshall in atrial fibrillation recurrences after catheter ablation: therapeutic effect of ethanol infusion. J Cardiovasc Electrophysiol. 2012 Jun;23(6):583-91. doi: 10.1111/j.1540-8167.2011.02268.x. Epub 2012 Mar 19.

Reference Type BACKGROUND
PMID: 22429895 (View on PubMed)

Pambrun T, Denis A, Duchateau J, Sacher F, Hocini M, Jais P, Haissaguerre M, Derval N. MARSHALL bundles elimination, Pulmonary veins isolation and Lines completion for ANatomical ablation of persistent atrial fibrillation: MARSHALL-PLAN case series. J Cardiovasc Electrophysiol. 2019 Jan;30(1):7-15. doi: 10.1111/jce.13797. Epub 2018 Dec 21.

Reference Type RESULT
PMID: 30461121 (View on PubMed)

Rivard L, Hocini M, Rostock T, Cauchemez B, Forclaz A, Jadidi AS, Linton N, Nault I, Miyazaki S, Liu X, Xhaet O, Shah A, Sacher F, Derval N, Jais P, Khairy P, Macle L, Nattel S, Willems S, Haissaguerre M. Improved outcome following restoration of sinus rhythm prior to catheter ablation of persistent atrial fibrillation: a comparative multicenter study. Heart Rhythm. 2012 Jul;9(7):1025-30. doi: 10.1016/j.hrthm.2012.02.016. Epub 2012 Feb 15.

Reference Type RESULT
PMID: 22342863 (View on PubMed)

Boveda S, Metzner A, Nguyen DQ, Chun KRJ, Goehl K, Noelker G, Deharo JC, Andrikopoulos G, Dahme T, Lellouche N, Defaye P. Single-Procedure Outcomes and Quality-of-Life Improvement 12 Months Post-Cryoballoon Ablation in Persistent Atrial Fibrillation: Results From the Multicenter CRYO4PERSISTENT AF Trial. JACC Clin Electrophysiol. 2018 Nov;4(11):1440-1447. doi: 10.1016/j.jacep.2018.07.007. Epub 2018 Aug 25.

Reference Type RESULT
PMID: 30466850 (View on PubMed)

Su WW, Reddy VY, Bhasin K, Champagne J, Sangrigoli RM, Braegelmann KM, Kueffer FJ, Novak P, Gupta SK, Yamane T, Calkins H; STOP Persistent AF Investigators. Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial. Heart Rhythm. 2020 Nov;17(11):1841-1847. doi: 10.1016/j.hrthm.2020.06.020. Epub 2020 Jun 24.

Reference Type RESULT
PMID: 32590151 (View on PubMed)

Derval N, Duchateau J, Denis A, Ramirez FD, Mahida S, Andre C, Krisai P, Nakatani Y, Kitamura T, Takigawa M, Chauvel R, Tixier R, Pillois X, Sacher F, Hocini M, Haissaguerre M, Jais P, Pambrun T. Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation (Marshall-PLAN): Prospective, single-center study. Heart Rhythm. 2021 Apr;18(4):529-537. doi: 10.1016/j.hrthm.2020.12.023. Epub 2020 Dec 29.

Reference Type RESULT
PMID: 33383226 (View on PubMed)

Bortone AA, Marijon E, Limite LR, Lagrange P, Brigadeau F, Martins R, Durand C, Albenque JP; PACIFIC study group. Pulmonary vein isolation alone or in combination with substrate modulation after electrical cardioversion failure in patients with persistent atrial fibrillation: The PACIFIC trial: Study design. J Cardiovasc Electrophysiol. 2023 Feb;34(2):270-278. doi: 10.1111/jce.15761. Epub 2022 Dec 7.

Reference Type DERIVED
PMID: 36434797 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-A02291-40

Identifier Type: OTHER

Identifier Source: secondary_id

PACIFIC

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

EXPORT Randomized Trial
NCT07197931 NOT_YET_RECRUITING NA