AzTrials
AzTrials

Ventricular TachycardiaPhase 3VOM-R01NCT01898221

Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation

A Phase 3 study testing Ethanol and Ablation in people with Ventricular Tachycardia and Atrial Fibrillation, run by The Methodist Hospital Research Institute at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The broad, long-term objective of this project is to evaluate the therapeutic value of vein of Marshall (VOM) ethanol infusion when added to catheter ablation of atrial fibrillation (AF). AF is the most common sustained arrhythmia in adults, and it is a leading cause of stroke, disability and increased mortality. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Ventricular Tachycardia, Atrial Fibrillation
What is being tested?
Ethanol and Ablation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
343 participants
Where
12 sitesUnited States
Study dates
Oct 2013to Dec 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients between the ages of 21 and 85 years
  • Diagnosed with symptomatic persistent AF Documentation of history of AF for at least 6 months AF not spontaneously converting to sinus rhythm, persisting for ≥7 days Sinus rhythm after cardioversion is NOT exclusion, provided that≥2 episodes of persistent AF occurred in the previous 6 months
  • Resistant or intolerant to at least one class I, II, or III anti arrhythmic drugs (AAD)
  • Patients deemed candidates for radio frequency(RF) ablation of AF
  • Able and willing to comply with pre-, post-, and follow-up requirements.

Who cannot join

  • Patients with previous PVAI procedure or left heart ablation procedure.
  • Left atrial thrombus.
  • LA diameter greater than 65 mm on long axis parasternal view, or left atrial volume more than 200 cc by MRI or CT.
  • Left ventricular ejection fraction < 30%.
  • Cardiac surgery within the previous 180 days.
  • Expecting cardiac transplantation or other cardiac surgery within 180 days.
Show all 28Show fewer
  • Coronary percutaneous transluminal coronary angioplasty (PTCA)/stenting within the previous 90 days.
  • Documented history of a thrombi-embolic event within the previous 90 days.
  • Diagnosed atrial myxoma.
  • Significant restrictive, constrictive, or chronic obstructive pulmonary disease with chronic symptoms.
  • Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment
  • Women who are pregnant.
  • Acute illness or active infection at time of index procedure documented by either pain, fever, drainage, positive culture and/or leukocytosis (WBC > 11. 000 mm3) for which antibiotics have been or will be prescribed.
  • Creatinine> 2. 5 mg/dl (or > 221 μmol/L, except for patients in dialysis).
  • Unstable angina.
  • Myocardial infarction within the previous 60 days.
  • History of blood clotting or bleeding abnormalities.
  • Contraindication to anticoagulation.
  • Contraindication to computed tomography or MRI procedures.
  • Life expectancy less than 1 year.
  • Uncontrolled heart failure.
  • Presence of an intramural thrombus, tumor, or other abnormality that precludes catheter introduction or positioning.
  • Presence of a condition that precludes vascular access.
  • Institute for Natural Resources (INR) greater than 3. 5 within 24 hours of procedure.
  • Cannot be removed from antiarrhythmic drugs for reasons other than AF.
  • Unwilling or unable to provide informed consent.
  • Current reported alcoholism.
  • -

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • Emory University Hospital

    Atlanta, Georgia, 30308

  • Texas Cardiac Arrythmia Research Foundation

    Austin, Texas, 78705

  • University of Colorado School of Medicince, Denver

    Denver, Colorado, 80045

  • St. Luke's Hospital Duluth

    Duluth, Minnesota, 55802

  • BCM/CHI St. Luke's Hospital

    Houston, Texas, 77030

  • Houston Methodist

    Houston, Texas, 77030

  • Houston VAMC

    Houston, Texas, 77030

  • KUMC Research Institute

    Kansas City, Kansas, 66160

  • USC Los Angeles - Keck Hopsital

    Los Angeles, California, 90033

  • Arizona Heart Rhythm Center

    Phoenix, Arizona, 85013

  • Virginia Commonwealth University

    Richmond, Virginia, 23292

  • San Diego Cardiac Center

    San Diego, California, 92123

Other trials in United States

About this study

The broad, long-term objective of this project is to evaluate the therapeutic value of vein of Marshall (VOM) ethanol infusion when added to catheter ablation of atrial fibrillation (AF). AF is the most common sustained arrhythmia in adults, and it is a leading cause of stroke, disability and increased mortality. Catheter ablation - pulmonary vein (PV) antral isolation (PVAI)- can lead to cure, but is best suited for paroxysmal AF, in which ectopic beats arising from the pulmonary veins were shown to initiate AF. PVAI success is lower in persistent AF, in which the role of the cardiac autonomic system, particularly the intrinsic cardiac ganglia, is being increasingly recognized. Expanding the ablation lesions to include greater areas the left atrial (LA) anatomy marginally improves outcomes, but also leads to increases in procedural complexity and duration, need of repeat procedures, and complications such as atrial flutters, particularly perimitral flutter (PMF). The investigators have developed a technique to perform rapid ablation of atrial tissues in AF using ethanol infusion in the vein of Marshall (VOM), and have shown: 1) Effective, rapid and safe tissue ablation of LA tissue neighboring the LA ridge and left inferior PV; 2) Regional LA vagal denervation by reaching the intrinsic cardiac ganglia; and 3) Facilitation of cure of PMF by ablating most of the mitral isthmus.

The investigators propose to evaluate outcomes differences yielded by VOM ethanol when added to conventional PVAI. The specific aims are: #1.To assesses the impact of VOM ethanol infusion in procedure success when added to de novo catheter ablation of persistent AF. The investigators will randomize patients with persistent AF undergoing a first AF ablation to standard PVAI vs. a combined VOM ethanol infusion plus PVAI (VOM-PV) #2. To assess the impact of VOM ethanol infusion added to repeat catheter ablation of recurrent AF after a failed ablation. Patients undergoing a repeat procedure for persistent AF after a failed PVAI will be randomized to either PVAI or VOM-PV as their repeat procedure. End points will include freedom from symptomatic or electrocardiographic AF after 12-15 months.

Read the detailed description

Although the risk of stroke is comparable in persistent and paroxysmal AF, the prevalence of persistent AF increases dramatically with increasing age, and thus is an overall more significant cause of morbidity and mortality. In the United States, there are currently an estimated 3.0 million adults with AF, and this number is expected to double in the next 25 years. Hospitalizations with a primary diagnosis of AF are close to half a million per year, which generates a tremendous economic burden on the health care system. When compared to health care costs of non-AF control subjects, patients with AF have greater annual healthcare costs (up to $8705 total annual incremental cost). On the basis of current prevalence data, it is estimated that AF leads to a national incremental health care cost of up to $26 billion. Inadequacy of pharmacological treatment options for persistent AF Management strategies are directed at heart rate control and stroke prevention -mere palliation- or at rhythm control. It has been shown that rhythm control strategies using antiarrhythmic drugs offer no benefit in elderly patients or patients with heart failure. Most of the lack of benefit of such rhythm control strategy is thought to be due to the adverse effects and suboptimal efficacy of antiarrhythmic drugs that can potentially augment mortality. Indeed, preservation of normal sinus rhythm is associated with decreased mortality. Dronedarone, the only antiarrhythmic drug shown to improve outcomes in nonpermanent AF compared to placebo, has been shown to double mortality, stroke and hospitalization for heart failure in the PALLAS study in patients with permanent. Thus, antiarrhythmic drugs remain suboptimal at best for the treatment of AF.

Shortcomings of catheter ablation of persistent AF Weak mechanistic rationale: Isolation of the pulmonary vein (PVs2) and adjacent LA (PV antrum) is the accepted procedural endpoint, based on the mechanistic concept that atrial extrasystoles arising from the PVs initiate paroxysmal AF. Other, non-PV triggers have been demonstrated.36 The link between PV extra systoles and AF is clear in paroxysmal AF, but not in persistent AF, in which the mechanisms of AF seem to be related more to a chronic atrial substrate than to acute triggers.4 Indeed, intramural reentry in the posterior LA seems to be particularly relevant in chronic models of AF. In persistent AF, the procedure has evolved, rather simplistically, to include additional lesions -besides isolation of the PVs, variably placed in the posterior wall, LA roof, and towards the mitral annulus, the superior vena cava,44 left atrial appendage, and other areas where complex fractionated atrial electrograms (CFAE) may be mapped. This brute force approach of simply destroying more tissue has yielded additional success, but new procedural targets with solid mechanistic bases are needed.

Suboptimal success and need for repeat procedures. Despite the additional tissue destruction, ablation success in persistent AF is with much lower than in paroxysmal AF, with single procedure success reported as low as 27%, 36%, or 49%, but up to 61% or 67%, depending on study heterogeneities in: definitions of persistent AF and of recurrence of AF, the type of AF monitoring, and ablation technique and operator experience. In order to achieve overall acceptable success rates, (which can reach up to 79%-94%), there is a consistent need for repeat procedures (sometimes up to 4) and the concomitant use of antiarrhythmic drugs. The rate of repeat procedures in experienced centers can reach up to 70 to 80%.PMF after catheter ablation of persistent AF. Clinical failures of a first ablation procedure are caused, in a significant portion of patients, by atrial flutters, rather than recurrent AF, and recurrence as flutter portends a greater chance of success in a second procedure. Such atrial flutters may be caused by perimitral reentry in up to 33-60% of the patients. Catheter ablation of PMF involves the creation of a linear lesion from the mitral annulus to the left inferior PV (the so-called mitral isthmus).Achieving a complete ablation (defined by bidirectional conduction block across the ablation line) can be very difficult, with success rates reported as 32%, 64%, or 71%. It sometimes requires ablation inside the coronary sinus (CS), in close proximity to the circumflex coronary artery, which could be damaged of note, incomplete ablation of the mitral isthmus is proarrhythmogenic, increasing the risk of recurrent flutter by up to 4 times.

Being tested
Ethanol, Ablation
Medical subject headings
Tachycardia, Ventricular, Atrial Fibrillation

What participants receive

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

  • EthanolDrug

    Also called Alcohol

    We enter the CS with a sheath advanced from the right internal jugular vein. A sub-selector catheter with a ~90° angle at the tip (typically, a left internal mammary artery angioplasty guide catheter) is advanced through the CS sheath with its tip pointing superiorly and posteriorly.

  • AblationProcedure or surgery

    Also called standard catheter ablation procedure,

    The doctor will perform only the standard procedure. Throughout the procedure, the researchers will document the following information for ALL patients: measurements such as whether the treatment was successful or unsuccessful, X-ray exposure time, procedure time, whether there were any complications, and other general procedural measurements.

Study groups in NCT01898221
Study groupRoleWhat they receive
Randomized to VOM-PV.ExperimentalRandomized to vein of marshal ethanol infusion plus conventional pulmonary vein antral isolation (VOM-PV) to treat persistent atrial fibrillation
Receives: Drug: Ethanol; Procedure: Ablation
Randomized to conventional PVAI.Active comparatorConventional pulmonary vein antral isolation (PVAI) to treat persistent atrial fibrillation
Receives: Procedure: Ablation

What is being measured

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

  1. Amount of Treated Subjects With Freedom of Symptomatic Post-procedural AF or Flutter at 12 and 15 Months Post Procedure and Less Than 1 Min/Day of AF or Flutter on 4-week EKG Monitor.

    Primary Endpoints:

    The primary outcome is freedom from symptomatic post-procedural AF or flutter at 12 and 15 months from the procedure and less than 1 min/day of AF or flutter on 4-week EKG monitor.

    Measured: 15 months

Secondary outcomes (1)
  1. Number of Patients With Clinical Success

    Freedom from AF/AT after >1 procedure.

    Measured: 90 days

Timeline

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

  1. First posted12 Jul 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionDec 2019
  4. Study completionDec 2019

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects who meet inclusion criteria will be randomized to either a conventional PVAI or PVAI with VOM procedure.
Masking
Single blind
Who is masked
Participant
Enrolment
343 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01898221
Sponsor's protocol ID
Pro00008380
Other IDs
1R01HL115003-01A1
Acronym
VOM-R01
Status last verified
Aug 2025
First submitted
28 May 2013
Last updated
21 Aug 2025
Data monitoring committee
Yes
Individual data sharing
No: Individual participant data is not planned for sharing at this time.

Publications

  • 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
  • Valderrabano M, Peterson LE, Swarup V, Schurmann PA, Makkar A, Doshi RN, DeLurgio D, Athill CA, Ellenbogen KA, Natale A, Koneru J, Dave AS, Giorgberidze I, Afshar H, Guthrie ML, Bunge R, Morillo CA, Kleiman NS. Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial. JAMA. 2020 Oct 27;324(16):1620-1628. doi: 10.1001/jama.2020.16195.

    PubMed 33107945

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ethanol and Ablation in people with Ventricular Tachycardia and Atrial Fibrillation, run by The Methodist Hospital Research Institute at 12 sites in United States.

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 28 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 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Amount of Treated Subjects With Freedom of Symptomatic Post-procedural AF or Flutter at 12 and 15 Months Post Procedure and Less Than 1 Min/Day of AF or Flutter on 4-week EKG Monitor. (time frame: 15 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 NCT01898221, 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 21 Aug 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in