Atrial FibrillationMARSHALL-PLANNCT04681872
Marshall Ethanolization, Pulmonary Vein Isolation and Line Completion for Ablation of Persistent Atrial Fibrillation
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 9 sites in 2 countries.
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
- 262 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 20 Sep 2021to 20 Sep 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 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 and ablation of atrial fibrillation defined as: history of symptomatic persistent atrial fibrillation in the past year documented by ECG,
- 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
- 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 products (history of major immediate reaction, thyrotoxicosis),
- Ethanol hypersensitivity,
- Unstable angina or ongoing myocardial ischemia,
Show all 13Show fewer
- Myocardial infarction within 3 months prior to inclusion,
- Congenital heart disease, where the underlying abnormality increases the ablation risk,
- Severe bleeding, clotting or thrombotic disorder,
- Hypertrophic cardiomyopathy defined by a left ventricular septum thickness > 1.5 cm,
- Pregnant, parturient or nursing women,
- Person unable to give informed consent,
- Patient detained by judicial or administrative order, patient under legal protection (guardianship, curators, safeguarding justice).
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
France8 sites
Clinique Saint Augustin
Bordeaux, 33074
Clermont-Ferrand University Hospital
Clermont-Ferrand, 63003
Ambroise Paré Hospital
Neuilly-sur-Seine, 92200
Les Franciscaines Hospital
Nîmes, 30032
Bordeaux University Hospital
Pessac, 33604
Centre Cardiologique du Nord
Saint-Denis, 93200
Clinique Pasteur
Toulouse, 31076
Toulouse University Hospirtal
Toulouse, 31400
About this study
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).
Read the detailed description
Atrial fibrillation (AF) characterized by a fast and anarchic electrical activation of the atria, results in uncoordinated and inefficient atrial contractions that increases the risks of heart failure and strokes. Besides being a major source of morbidity and mortality, AF is one of the most common heart condition and its prevalence increases with age. Radiofrequency catheter ablation of AF has become one of the treatment of choice in AF resistant to conventional antiarrhythmic drugs. For paroxysmal AF, the ablation strategy is clear and consists in complete pulmonary veins isolation (PVI). However, if this strategy works well in paroxysmal AF, the recurrences rate remains high in persistent AF. Beyond PVI, the ablation strategy that has prevailed over the past two decades remains controversial: the left atrium partition using linear lesions ("cox-maze" strategy); the mapping of the left atrium in AF to identify and localize the arrhythmia sources. Both methods have, besides favoring atrial flutters, failed to demonstrated superiority compared to PVI alone (as showed by the clinical trial STAR AF 2). The investigators aims to test a new method of ablation for patients suffering from persistent AF in order to decrease post ablation recurrence. They propose a strategy targeting the native structures facilitating reentries including the ligament of Marshall (LOM), an embryological remnant. Indeed, two studies have demonstrated that 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. To date, ablation techniques do not ensure the complete destruction of the 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. This innovative approach will then consist in 3 consecutive steps: 1) the destruction of Marshall bundles by ethanol infusion followed by the ablation of the distal and proximal muscular ramification (coronary sinus and ridge); 2) the standard PV isolation; 3) the linear lesions: the mitral, the roof and of the cavo-tricuspid isthmus, main causes of recurrence in atrial flutter.
- 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, Ethanolization, 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 Atrial Tachycardia (AT) greater than 30 seconds with or without antiarrhythmic medications after a single ablation procedure
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 2 years with or without antiarrhythmic medications after a single ablation procedure. Recurrences will be identified through transtelephonic electrocardiogram (ECG) monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Secondary outcomes (9)
Recurrence of AF or AT greater than 30 seconds after multiple ablation procedures
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure, at 2 years after multiple ablation procedures. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Recurrence of AF or AT greater than 30 seconds after a single ablation procedure (1)
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure, at 2 years, will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Recurrence of AF greater than 30 seconds after a single ablation procedure (2)
Recurrence rate (percentage) of AF > 30 seconds after the blanking period of 3-months post procedure, at 2 years after a single ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Recurrence of AF greater than 30 seconds after multiple ablation procedure.
Recurrence rate (percentage) of AF > 30 seconds after the blanking period of 3-months post procedure, at 2 years after a multiple ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after a single ablation procedure.
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure at 2-years without antiarrhythmic medications after a single ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after multiple ablation procedure.
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure at 2-years without antiarrhythmic medications after multiple ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms.
Measured: 2 years
Proportion of patients under antiarrhythmic medications
Percentage of patients
Measured: 2 years
Proportion of patients with repeated procedures
Percentage of patients
Measured: up to 2 years
Incidence of periprocedural complications
Percentage of periprocedural complications : transient ischemic attack or stroke, cardiac tamponade, atrioesophageal fistula, pericarditis, complications at access site (hematoma, arteriovenous fistula, pseudoaneurysm)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start20 Sep 2021
- Primary completion20 Sep 2027 (estimated)
- Study completion20 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- 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, multicenter clinical trial of superiority
- Masking
- None (open label)
- Enrolment
- 262 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, BordeauxAntoine BENARD, MD, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04681872
- Sponsor's protocol ID
- CHUBX 2019/55
- Acronym
- MARSHALL-PLAN
- Status last verified
- Jun 2025
- First submitted
- 18 Dec 2020
- Last updated
- 1 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Derval N, Tixier R, Duchateau J, Georget A, Albenque JP, Combes S, Massoullie G, Zhao A, Cauchemez B, Knecht S, Duytschaever M, Escande W, Lepillier A, Denis A, Chauvel R, Bortone A, Maury P, Sacristan B, Charton J, Sacher F, Hocini M, Haissaguerre M, Jais P, Benard A, Pambrun T. Marshall-Plan ablation strategy versus pulmonary vein isolation in persistent atrial fibrillation: Clinical trial design. Am Heart J. 2026 Aug;298:107442. doi: 10.1016/j.ahj.2026.107442. Epub 2026 Apr 6.
PubMed 41951089
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Marshall Ethanolization, Pulmonary Vein Isolation and Line Completion for Ablation of Persistent Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT04681872
- Acronym / sponsor ID
- MARSHALL-PLAN / CHUBX 2019/55
- Conditions
- Atrial Fibrillation
- Keywords
- Persistent atrial fibrillation, Pulmonary vein isolation, Catheter ablation, Ethanolization, Ligament of Marshall
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 262 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 20 Sep 2021 (actual)
- Primary completion
- 20 Sep 2027 (estimated)
- Study completion
- 20 Sep 2027 (estimated)
- First posted
- 23 Dec 2020 (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).
Detailed description
Atrial fibrillation (AF) characterized by a fast and anarchic electrical activation of the atria, results in uncoordinated and inefficient atrial contractions that increases the risks of heart failure and strokes. Besides being a major source of morbidity and mortality, AF is one of the most common heart condition and its prevalence increases with age. Radiofrequency catheter ablation of AF has become one of the treatment of choice in AF resistant to conventional antiarrhythmic drugs. For paroxysmal AF, the ablation strategy is clear and consists in complete pulmonary veins isolation (PVI). However, if this strategy works well in paroxysmal AF, the recurrences rate remains high in persistent AF. Beyond PVI, the ablation strategy that has prevailed over the past two decades remains controversial: the left atrium partition using linear lesions ("cox-maze" strategy); the mapping of the left atrium in AF to identify and localize the arrhythmia sources. Both methods have, besides favoring atrial flutters, failed to demonstrated superiority compared to PVI alone (as showed by the clinical trial STAR AF 2). The investigators aims to test a new method of ablation for patients suffering from persistent AF in order to decrease post ablation recurrence. They propose a strategy targeting the native structures facilitating reentries including the ligament of Marshall (LOM), an embryological remnant. Indeed, two studies have demonstrated that 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. To date, ablation techniques do not ensure the complete destruction of the 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. This innovative approach will then consist in 3 consecutive steps: 1) the destruction of Marshall bundles by ethanol infusion followed by the ablation of the distal and proximal muscular ramification (coronary sinus and ridge); 2) the standard PV isolation; 3) the linear lesions: the mitral, the roof and of the cavo-tricuspid isthmus, main causes of recurrence in atrial flutter.
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, multicenter 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 (5 listed)
- Age > 18 years of both genders
- Suitable candidate for catheter and ablation of atrial fibrillation defined as: history of symptomatic persistent atrial fibrillation in the past year documented by ECG,
- 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 (13 listed)
- 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 products (history of major immediate reaction, thyrotoxicosis),
- Ethanol hypersensitivity,
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 Atrial Tachycardia (AT) greater than 30 seconds with or without antiarrhythmic medications after a single ablation procedure
Time frame: 2 years
Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 2 years with or without antiarrhythmic medications after a single ablation procedure. Recurrences will be identified through transtelephonic electrocardiogram (ECG) monitor with weekly transmitted ECG and at any time in case of symptoms.
9 secondary outcomes
Recurrence of AF or AT greater than 30 seconds after multiple ablation procedures
Time frame: 2 years
Recurrence of AF or AT greater than 30 seconds after a single ablation procedure (1)
Time frame: 2 years
Recurrence of AF greater than 30 seconds after a single ablation procedure (2)
Time frame: 2 years
Recurrence of AF greater than 30 seconds after multiple ablation procedure.
Time frame: 2 years
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after a single ablation procedure.
Time frame: 2 years
Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after multiple ablation procedure.
Time frame: 2 years
Proportion of patients under antiarrhythmic medications
Time frame: 2 years
Proportion of patients with repeated procedures
Time frame: up to 2 years
Incidence of periprocedural complications
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
- Derived from this study: PubMed 41951089Derval N, Tixier R, Duchateau J, Georget A, Albenque JP, Combes S, Massoullie G, Zhao A, Cauchemez B, Knecht S, Duytschaever M, Escande W, Lepillier A, Denis A, Chauvel R, Bortone A, Maury P, Sacristan B, Charton J, Sacher F, Hocini M, Haissaguerre M, Jais P, Benard A, Pambrun T. Marshall-Plan ablation strategy versus pulmonary vein isolation in persistent atrial fibrillation: Clinical trial design. Am Heart J. 2026 Aug;298:107442. doi: 10.1016/j.ahj.2026.107442. Epub 2026 Apr 6.
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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
Antoine BENARD, MD study chair
University Hospital, Bordeaux
9 sites in 2 countries: 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 9 sites in 2 countries.
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 5 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Belgium. 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?
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 Atrial Tachycardia (AT) greater than 30 seconds with or without antiarrhythmic medications after a single ablation procedure (time frame: 2 years). 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 NCT04681872, which also lists 1 linked publication.
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 1 Jul 2025; AzTrials last refreshed its copy on 2 Nov 2026.