Atrial FibrillationPLAN-MARSHALLNCT04206982
MARSHALL PLAN Vs. Pulmonary Veins Isolation Monocentric Trial
A study testing Destruction of Marshall bundles, Pulmonary veins isolation and Linear ablation in the left and right atria in people with Atrial Fibrillation, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Destruction of Marshall bundles, Pulmonary veins isolation and Linear ablation in the left and right atria
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 22 Jan 2020to 23 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MARSHALL Bundles Elimination, Pulmonary Veins Isolation and Lines Completion for ANatomical Ablation of Persistent Atrial Fibrillation Versus Pulmonary Veins Isolation: The MARSHALL PLAN Monocentric Trial
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.
Read the 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
- Being tested
- Destruction of Marshall bundles, Pulmonary veins isolation, Linear ablation in the left and right atria
- Keywords
- Persistent atrial fibrillation, Pulmonary vein isolation, Catheter ablation, Ethanolisation, Ligament of Marshall
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Destruction of Marshall bundlesProcedure or surgery
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 isolationProcedure or surgery
Achievement of a wide disconnection of the right and left pulmonary veins.
Linear ablation in the left and right atriaProcedure or surgery
Ablation of the mitral, the roof, and the cavo-tricuspid isthmus.
| Study group | Role | What they receive |
|---|---|---|
| Marshall Plan arm | Experimental | 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. Receives: Procedure: Destruction of Marshall bundles; Procedure: Pulmonary veins isolation; Procedure: Linear ablation in the left and right atria |
| Pulmonary vein isolation arm | Active comparator | Not described Receives: Procedure: Pulmonary veins isolation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of AF or AT greater than 30 seconds with or without antiarrhythmic medications.
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 12 months with or without antiarrhythmic medications. Recurrences will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 12 months
Secondary outcomes (9)
Recurrence of AF greater than 30 seconds
Recurrence rate (percentage) of AF greater than 30 seconds after the blanking period of 3-months post procedure at 12 months. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 12 months
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 12 months without antiarrhythmic medications. Recurrences will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 12 months
Rate of patients under antiarrhythmic medications
Percentage of patients
Measured: 12 months
Number of patients with repeat procedures
Number of patients
Measured: 12 months
Rate of periprocedural complications
Percentage of transient ischemic attack or stroke, cardiac tamponade, atrio-oesophageal fistula, pericarditis, complications at access site (hematoma, arteriovenous fistula, pseudoaneurysm).
Measured: 12 months
AF discontinuation rate during procedure
Percentage of AF discontinuation
Measured: 12 months
Per-procedure AF / AT inducibility rate
Percentage of per-procedure AF / AT inducibility
Measured: 12 months
Mitral line block rate
Percentage of mitral line block according to consensus block criteria
Measured: 12 months
Radiofrequency duration necessary for pulmonary veins isolation
Duration measured in seconds
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start22 Jan 2020
- Primary completion23 Nov 2023
- Study completion23 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The Marshall Plan is a prospective randomized, parallel-group, monocentric clinical trial of superiority.
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas DERVAL, MD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206982
- Sponsor's protocol ID
- CHUBX 2019/08
- Acronym
- PLAN-MARSHALL
- Status last verified
- Jun 2025
- First submitted
- 18 Dec 2019
- Last updated
- 17 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 19756206Derval 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.
PubMed 40392905
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MARSHALL Bundles Elimination, Pulmonary Veins Isolation and Lines Completion for ANatomical Ablation of Persistent Atrial Fibrillation Versus Pulmonary Veins Isolation: The MARSHALL PLAN Monocentric Trial
- ClinicalTrials.gov ID
- NCT04206982
- Acronym / sponsor ID
- PLAN-MARSHALL / CHUBX 2019/08
- Conditions
- Atrial Fibrillation
- Keywords
- Persistent atrial fibrillation, Pulmonary vein isolation, Catheter ablation, Ethanolisation, Ligament of Marshall
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 23 Nov 2023 (actual)
- Study completion
- 23 Nov 2023 (actual)
- First posted
- 20 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The Marshall Plan is a prospective randomized, parallel-group, monocentric clinical trial of superiority.
| Arm | Type | Receives |
|---|---|---|
| Marshall Plan arm | Experimental | Procedure: Destruction of Marshall bundles, Procedure: Pulmonary veins isolation, Procedure: Linear ablation in the left and right atriaPatients 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. |
| Pulmonary vein isolation arm | Active comparator | Procedure: Pulmonary veins isolation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age > 18 years of both genders
- Suitable candidate for catheter non-emergent mapping and ablation of atrial fibrillation defined as:
- 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
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Destruction of Marshall bundlesDestruction 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. | Procedure or surgery | Marshall Plan arm |
| Pulmonary veins isolationAchievement of a wide disconnection of the right and left pulmonary veins. | Procedure or surgery | Marshall Plan arm, Pulmonary vein isolation arm |
| Linear ablation in the left and right atriaAblation of the mitral, the roof, and the cavo-tricuspid isthmus. | Procedure or surgery | Marshall Plan arm |
Primary outcome
Recurrence of AF or AT greater than 30 seconds with or without antiarrhythmic medications.
Time frame: 12 months
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 12 months with or without antiarrhythmic medications. Recurrences will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
9 secondary outcomes
Recurrence of AF greater than 30 seconds
Time frame: 12 months
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications
Time frame: 12 months
Rate of patients under antiarrhythmic medications
Time frame: 12 months
Number of patients with repeat procedures
Time frame: 12 months
Rate of periprocedural complications
Time frame: 12 months
AF discontinuation rate during procedure
Time frame: 12 months
Per-procedure AF / AT inducibility rate
Time frame: 12 months
Mitral line block rate
Time frame: 12 months
Radiofrequency duration necessary for pulmonary veins isolation
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2025.
- Results publication: PubMed 19756206Valderrabano 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.
- Derived from this study: PubMed 40392905Derval 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas DERVAL, MD principal investigator
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Destruction of Marshall bundles, Pulmonary veins isolation and Linear ablation in the left and right atria in people with Atrial Fibrillation, run by University Hospital, Bordeaux at 1 site 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 7 inclusion and 20 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: finished, as of the sponsor's last update on 17 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence of AF or AT greater than 30 seconds with or without antiarrhythmic medications. (time frame: 12 months). 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 NCT04206982, which also lists 2 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 17 Jun 2025.