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Persistent Atrial FibrillationPACIFICNCT05264831

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

A study testing Pulmonary Vein Isolation (PVI) alone and PVI procedure associated with substrate modulation in people with Persistent Atrial Fibrillation, run by Elsan at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Persistent Atrial Fibrillation
What is being tested?
Pulmonary Vein Isolation (PVI) alone and PVI procedure associated with substrate modulation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
450 participants
Where
13 sitesFrance
Study dates
20 Feb 2023to 1 Oct 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 :
  • 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:
  • Life expectancy > 5 years;
Show all 11Show fewer
  • Female or male between 18 and 80 years of age at the electric cardioversion time
  • Affiliation to a health insurance system;
  • 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):
  • Patient with failed electric cardioversion i.e. in AF, confirmed by ECG.

Who cannot join

  • Criteria to be validated before or after performing electric cardioversion (the study cannot be proposed to patients corresponding to these criteria):
  • Current hyperthyroidism;
  • Pregnant or breastfeeding woman;
  • Patient with a Body Mass Index (BMI) greater than 35;
  • Patient with severe Chronic Obstructive Pulmonary Disease (COPD);
  • Patient with hypertrophic heart disease;
Show all 21Show fewer
  • Patient with a mechanical or biological mitral valve;
  • Contraindications to anticoagulants;
  • Transient Ischemic Attack (TIA) /stroke less than 6 months old;
  • Psychiatric illness affecting follow-up;
  • Left Ventricular Ejection Fraction (LVEF) < 40% ;
  • Uncontrolled ischaemic heart disease (angina, myocardial ischaemia)
  • Patients under legal protection
  • Cardiac surgery on left atrium
  • Inflammatory status in progress (cancer, rheumatoid arthritis, PPRZ, acute or chronic periodontitis, Crohn's disease, RCUH)
  • Pulmonary embolism or phlebitis less than 6 months old
  • Prior atrial fibrillation ablation
  • Active cancer
  • Criteria to be validated before randomization, on the day of ablation (these patients cannot be randomized):
  • Patient in sinus rhythm 4-6 weeks after electric cardioversion: these patients are included in the study registry.
  • Patient with complete absence of sinus rhythm (less than 10 seconds) after 3 electric cardioversion attempts: these patients will discontinue from the study.

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Agustín Bortone, MD contact

04 66 26 63 75 ext. +33

agubene@hotmail.com

13 sites in 1 country

France13 sites, 12 recruiting

  • Infirmerie Protestante

    Caluire-et-Cuire, 69300

    Cyril Durand, MD

    Recruiting

  • CH Libourne

    Libourne, 33500

    Rim EL BOUAZZAOUI, MD

    Not yet recruiting

  • CHU Lille

    Lille, 59000

    Active, not recruiting

  • Hopital ST Phillbert

    Lomme, 59462

    Yves Guyomar, MD

    Not yet recruiting

  • CMC Ambroise Paré Hartmann

    Neuilly-sur-Seine, 92200

    Alexandre Zhao, MD

    Not yet recruiting

  • Hôpital Privé Les Franciscaines

    Nîmes, 30000

    Agustín Bortone, MD, agubene@hotmail.com

    Recruiting

  • Hôpital Européen Georges Pompidou Service de cardiologie - Unité rythmologie

    Paris, 75015

    Emilie Varlet, MD

    Recruiting

  • Clinique St Pierre Cardiologie

    Perpignan, 66000

    Philippe Lagrange, MD

    Recruiting

  • CHU Rennes

    Rennes, 35033

    Raphael Martins, MD

    Recruiting

  • CCN

    Saint-Denis, 93200

    Antoine Lepillier, MD

    Not yet recruiting

  • Clinique Rhéna

    Strasbourg, 67000

    Matjieu Schaaf, MD

    Not yet recruiting

  • Clinique Pasteur Service de cardiologie/rythmologie

    Toulouse, 31076

    Jean-Paul Albenque, MD

    Recruiting

  • Chu Nancy

    Vandœuvre-lès-Nancy, 54500

    Jean-Marc SELLAL, MD

    Not yet recruiting

Other trials in France

About this study

Official title: Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure in Patients With Persistent Atrial Fibrillation: a Randomized, Multicentric, and Comparative Study

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
Read the detailed description

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.

Being tested
Pulmonary Vein Isolation (PVI) alone, PVI procedure associated with substrate modulation
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pulmonary Vein Isolation (PVI) aloneProcedure or surgery

    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 associated with substrate modulationProcedure or surgery

    PVI procedure associated with substrate modulation

Study groups in NCT05264831
Study groupRoleWhat they receive
PVI procedure aloneActive comparatorIf 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
Receives: Procedure: Pulmonary Vein Isolation (PVI) alone
PVI procedure combined with substrate modulationExperimentalIf 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
Receives: Procedure: PVI procedure associated with substrate modulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1-year sinus rhythm maintenance rate

    Rate of patients with sinus rhythm (yes/no) at 1 year after a single ablative procedure

    Measured: At 1 year after ablation

Secondary outcomes (13)

  1. Rate of patients with sinus rhythm (randomized patients)

    Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure.

    Measured: At 1 year after ablation

  2. Rate of patients with sinus rhythm (registry patients)

    Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure.

    Measured: At 1 year after ablation

  3. Rate of patients with sinus rhythm (randomized and registry patients, strategy PVI procedure alone)

    Rate of patients with sinus rhythm during 1 year after ablation and after a single ablative procedure.

    Measured: At 1 year after ablation

  4. Duration (in minutes) of ablative procedure

    Duration (in minutes) of ablative procedure

    Measured: On the day of the ablative procedure

  5. Duration (in minutes) of radiofrequency use

    Duration (in minutes) of radiofrequency use

    Measured: On the day of the ablative procedure

  6. Duration (in minutes) of Fluoroscopy

    Duration (in minutes) of Fluoroscopy

    Measured: On the day of the ablative procedure

  7. Duration (in days) of hospitalization

    Duration (in days) of hospitalization

    Measured: From date of surgery until the date of discharge from hospital assessed up to 1 day

  8. Evaluation of major complications rate

    Tamponade and/or stroke rate out of the blanking period and up to 1-year follow-up

    Measured: Up to 1 year

  9. Evaluation of drug treatment use rate or electric cardioversion in the blanking period

    Number of patients using drug treatment and/or electric cardioversion during the blanking period (first 3 months after ablation) between the two strategies (randomized patients)

    Measured: At three months after ablation

  10. Evaluation of the minor complications rate between the two strategies after 1-year follow-up (randomized patients)

    Occurrence of a false aneurysm or fistulas at the puncture sites and/or occurrence of a post-ablation pericardial reaction

    Measured: up to 1-year follow-up

  11. Evaluation of the vein isolation as well as other linear lesions in patients with recurrence of atrial fibrillation during 1 year after ablation

    Pulmonary vein isolation as well as other linear lesions block assessment during redo procedures

    Measured: up to 1-year follow-up

  12. Evaluation of the impact of low voltage areas on the response to EC prior to catheter ablation

    Relationship between the presence or absence of LA low voltage areas and the response to EC prior to catheter ablation Relationship between the extent of LA low voltage areas and the response to EC prior to catheter ablation Relationship between the location of LA low voltage areas and the response to EC prior to catheter ablation

    Measured: catheter ablation

  13. Evaluation of the impact of low voltage areas on the success of the ablation procedure

    Relationship between the presence or absence of LA low voltage areas and the success of the ablation procedure Relationship between the extent of LA low voltage areas and the success of the ablation procedure Relationship between the location of LA low voltage areas and the success of the ablation procedure

    Measured: ablation procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2022
  2. Study start20 Feb 2023
  3. Primary completion1 Apr 2025 (estimated)
  4. Study completion1 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
450 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05264831
Sponsor's protocol ID
PACIFIC
Other IDs
2021-A02291-40
Acronym
PACIFIC
Status last verified
Apr 2024
First submitted
3 Feb 2022
Last updated
24 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 34520521

  • 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.

    PubMed 25946280

  • 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.

    PubMed 17341503

  • 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.

    PubMed 18614522

  • 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.

    PubMed 31279972

  • 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.

    PubMed 11028490

  • 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.

    PubMed 19756206

  • 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.

    PubMed 22429895

  • 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.

    PubMed 30461121

  • 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.

    PubMed 22342863

  • 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.

    PubMed 30466850

  • 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.

    PubMed 32590151

  • 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.

    PubMed 33383226

  • 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.

    PubMed 36434797

Questions about this trial

What is this clinical trial studying?

A study testing Pulmonary Vein Isolation (PVI) alone and PVI procedure associated with substrate modulation in people with Persistent Atrial Fibrillation, run by Elsan at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Agustín Bortone, MD (04 66 26 63 75 ext. +33, agubene@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1-year sinus rhythm maintenance rate (time frame: At 1 year after ablation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05264831, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2024.

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