Clinical trial NCT05264831: Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Persistent Atrial Fibrillation
Lead sponsor: Elsan
Sponsor class: OTHER
First posted: 2022-03-03
Enrollment: 450
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: 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 purpose: TREATMENT

Brief 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.

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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1-year sinus rhythm maintenance rate
timeFrame: At 1 year after ablation
Secondary outcomes:
measure: Rate of patients with sinus rhythm (randomized patients)
timeFrame: At 1 year after ablation
measure: Rate of patients with sinus rhythm (registry patients)
timeFrame: At 1 year after ablation
measure: Rate of patients with sinus rhythm (randomized and registry patients, strategy PVI procedure alone)
timeFrame: At 1 year after ablation
measure: Duration (in minutes) of ablative procedure
timeFrame: On the day of the ablative procedure
measure: Duration (in minutes) of radiofrequency use
timeFrame: On the day of the ablative procedure
measure: Duration (in minutes) of Fluoroscopy
timeFrame: On the day of the ablative procedure
measure: Duration (in days) of hospitalization
timeFrame: From date of surgery until the date of discharge from hospital assessed up to 1 day
measure: Evaluation of major complications rate
timeFrame: Up to 1 year
measure: Evaluation of drug treatment use rate or electric cardioversion in the blanking period
timeFrame: At three months after ablation
measure: Evaluation of the minor complications rate between the two strategies after 1-year follow-up (randomized patients)
timeFrame: up to 1-year follow-up
measure: Evaluation of the vein isolation as well as other linear lesions in patients with recurrence of atrial fibrillation during 1 year after ablation
timeFrame: up to 1-year follow-up
measure: Evaluation of the impact of low voltage areas on the response to EC prior to catheter ablation
timeFrame: catheter ablation
measure: Evaluation of the impact of low voltage areas on the success of the ablation procedure
timeFrame: ablation procedure
Other outcomes:
Locations:
city: Caluire Et Cuire
country: France
facility: Infirmerie Protestante
city: Libourne
country: France
facility: CH Libourne
city: Lille
country: France
facility: CHU Lille
city: Lomme
country: France
facility: Hopital ST Phillbert
city: Neuilly-sur-Seine
country: France
facility: CMC Ambroise Paré Hartmann
city: Nîmes
country: France
facility: Hôpital Privé Les Franciscaines
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou Service de cardiologie - Unité rythmologie
city: Perpignan
country: France
facility: Clinique St Pierre Cardiologie
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Denis
country: France
facility: CCN
city: Strasbourg
country: France
facility: Clinique Rhéna
city: Toulouse
country: France
facility: Clinique Pasteur Service de cardiologie/rythmologie
city: Vandœuvre-lès-Nancy
country: France
facility: Chu Nancy
Study officials:
affiliation: Elsan
name: Augustin Bortone, MD
role: STUDY_DIRECTOR
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