MARSHALL PLAN Vs. Pulmonary Veins Isolation Monocentric Trial

NCT ID: NCT04206982

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2023-11-23

Brief Summary

In ablation strategy for persistent Atrial Fibrillation (PsAF), ablation limited to Pulmonary Vein (PV) isolation is the most straightforward approach but the result give only 50% of arrhythmia free follow-up. Substrate modification strategies have failed to demonstrate their superiority with variable reported success rate. The Marshall network is a highly arrhythmogenic structure that has not been incorporated in current ablation strategies. The investigators sought to investigate a new ablation strategy that target systematically the vein of Marshall by ethanol infusion. This step is integrated in a new ablation strategy consisting in a global anatomical substrate based ablation including PV isolation and left atrial linear ablation (Marshall-Plan).

The main objective of this study is to compare the 12 month freedom from any arrhythmia (Atrial Fibrillation (AF)/Atrial Tachycardia (AT)) between the Marshall-Plan approach and the PV isolation approach.

Detailed Description

Ablation strategy for persistent AF besides pulmonary vein isolation remains controversial. Indeed, two approaches have prevailed over the past two decades "cox-maze" strategy and mapping of the left atrium but both methods have failed to decrease AF recurrences (as shown by the clinical trial STAR AF 2). Two studies have demonstrated that the ligament of Marshall (LOM) could be the source of focal activities, the substrate of reentries and a strong parasympathetic modulator. For these reasons, LOM may represent a major target in AF treatment besides PV isolation. Nevertheless, conventional ablation techniques do not ensure the complete destruction of Marshall's musculature and parasympathetic ganglia that surround it, largely isolated by a sheath of adipose tissue. To overcome this technical limitation, LOM elimination can be achieved by alcohol injection into the vein of Marshall.The investigator innovative approach called Marshall Plan will then consists in 3 steps: 1) the destruction of Marshall bundles by ethanol infusion followed by the ablation of the distal Coronary Sinus (CS) bundles, the ridge and the saddle; 2) the standard PV isolation; 3) and finally ablation of the mitral line, the roof and of the cavo-tricuspid isthmus, main causes of recurrence in atrial flutter.

Before ablation procedure patients will be randomized in 2 arms: Marshall Plan (treatment arm) or pulmonary vein isolation (control arm). Patients will be followed at 3, 6, 9 and 12 months in-office visits or hospitalization. Patients will have different tests: electrocardiogram (ECG), cardiac echography, stress test, 24hours Holter and transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Marshall Plan arm

Patients will undergo (1) the destruction of Marshall bundles by ethanol infusion followed by ablation of the distal coronary sinus bundles, the ridge and the saddle; (2) the standard pulmonary veins sleeves isolation; (3) and finally the ablation of the mitral, the roof, and the cavo-tricuspid isthmus.

Group Type: EXPERIMENTAL

Destruction of Marshall bundles

Intervention Type: PROCEDURE

Destruction of Marshall bundles by ethanol 96% infusion (2 separate injections of 5ml on 1 minute each) followed by ablation of the distal coronary sinus bundles, the ridge and the saddle.

Pulmonary veins isolation

Intervention Type: PROCEDURE

Achievement of a wide disconnection of the right and left pulmonary veins.

Linear ablation in the left and right atria

Intervention Type: PROCEDURE

Ablation of the mitral, the roof, and the cavo-tricuspid isthmus.

Pulmonary vein isolation arm

Group Type: ACTIVE_COMPARATOR

Pulmonary veins isolation

Intervention Type: PROCEDURE

Achievement of a wide disconnection of the right and left pulmonary veins.

Interventions

Destruction of Marshall bundles

Destruction of Marshall bundles by ethanol 96% infusion (2 separate injections of 5ml on 1 minute each) followed by ablation of the distal coronary sinus bundles, the ridge and the saddle.

Intervention Type: PROCEDURE

Pulmonary veins isolation

Achievement of a wide disconnection of the right and left pulmonary veins.

Intervention Type: PROCEDURE

Linear ablation in the left and right atria

Ablation of the mitral, the roof, and the cavo-tricuspid isthmus.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age > 18 years of both genders
• Suitable candidate for catheter non-emergent mapping and ablation of atrial fibrillation defined as:

• History of symptomatic persistent atrial fibrillation in the past year documented by ECG AND
• Treatment failure by at least one class of anti-arrhythmic medications (I-IV) (intolerance or recurrence of symptomatic AF)
• Patient affiliated or beneficiary of social security scheme
• Free, informed and written consent signed by the participant and the principal investigator (at least at the inclusion date and before all exams required for the clinical research)
• Effective contraception for women of childbearing potential

Exclusion Criteria

• Minor
• Prior left atrial heart ablation procedure
• Documented left atrial thrombus or another abnormality which precludes catheter introduction
• Contraindication to anticoagulation therapy (heparin, warfarin, or Novel Oral Anticoagulant (NOAC)
• Contraindication to iodinated contrast product XENETIX® (iobitridol hypersensitivity or at one of these excipients, history of major immediate reaction or cutaneous reaction to XENETIX® infusion, thyrotoxicosis)
• Hypersensitivity to ethanol
• Unstable angina or ongoing myocardial ischemia
• Myocardial infarction within 3 months prior to inclusion
• Congenital heart disease, where the underlying abnormality increases the ablation risk
• Pulmonary hypertension (pulmonary arterial hypertension > 50 mmHg)
• Severe uncontrolled systemic hypertension with systolic blood pressure (SBP) > 200 mm Hg within 30 days prior to inclusion
• Severe bleeding, clotting or thrombotic disorder
• Left atrial diameter > 60 mm (parasternal view)
• Hypertrophic cardiomyopathy defined by a left ventricular septum thickness > 1.5 cm
• Pregnant, parturient or nursing women
• Unable or unwilling to provide written informed consent
• Patient detained by judicial or administrative order
• Patient under psychiatric care
• Patient admitted in a social or healthcare establishment for any purpose other than the research
• Subject to a legal protection order (guardianship, patient under legal protection)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolas DERVAL, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

Bordeaux University Hospital

Pessac, , France

Countries

France

References

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)

Derval N, Tixier R, Duchateau J, Bouteiller X, Loock T, Denis A, Chauvel R, Bouyer B, Arnaud M, Yokoyama M, Kowalewski C, Monaco C, Ascione C, Sacher F, Hocini M, Jais P, Haissaguerre M, Pambrun T. Marshall-Plan Ablation Strategy Versus Pulmonary Vein Isolation in Persistent AF: A Randomized Controlled Trial. Circ Arrhythm Electrophysiol. 2025 May;18(5):e013427. doi: 10.1161/CIRCEP.124.013427. Epub 2025 May 20.

Reference Type: DERIVED

PMID: 40392905 (View on PubMed)

Other Identifiers

CHUBX 2019/08

Identifier Type: -

Identifier Source: org_study_id