Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation

NCT01898221 | Completed Phase 3 Results DMC

• 2 other identifiers: Pro000083801R01HL115003-01A1
• Study Type: interventional
• Target: 343
• Locations: 1 country
• Sites: 12

Brief 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. 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.

Conditions

Ventricular Tachycardia; Atrial Fibrillation

Outcome Measures

Primary Outcomes (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.

  15 months

Secondary Outcomes (1)

• Number of Patients With Clinical Success

  90 days

Study Arms (2)

Randomized to VOM-PV.

EXPERIMENTAL

Randomized to vein of marshal ethanol infusion plus conventional pulmonary vein antral isolation (VOM-PV) to treat persistent atrial fibrillation

Drug: Ethanol; Procedure: Ablation

Randomized to conventional PVAI.

ACTIVE COMPARATOR

Conventional pulmonary vein antral isolation (PVAI) to treat persistent atrial fibrillation

Procedure: Ablation

Interventions

Ethanol DRUG

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.

Also known as: Alcohol

Randomized to VOM-PV.

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.

Also known as: standard catheter ablation procedure,

Randomized to VOM-PV.; Randomized to conventional PVAI.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients between the ages of 21 and 85 years
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (12)

Arizona Heart Rhythm Center

Phoenix, Arizona, 85013, United States

Location

USC Los Angeles - Keck Hopsital

Los Angeles, California, 90033, United States

Location

San Diego Cardiac Center

San Diego, California, 92123, United States

Location

University of Colorado School of Medicince, Denver

Denver, Colorado, 80045, United States

Location

Emory University Hospital

Atlanta, Georgia, 30308, United States

Location

KUMC Research Institute

Kansas City, Kansas, 66160, United States

Location

St. Luke's Hospital Duluth

Duluth, Minnesota, 55802, United States

Location

Texas Cardiac Arrythmia Research Foundation

Austin, Texas, 78705, United States

Location

BCM/CHI St. Luke's Hospital

Houston, Texas, 77030, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Houston VAMC

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23292, United States

Location

Related Publications (2)

• 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.

  PMID: 22429895 BACKGROUND

• 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.

  PMID: 33107945 DERIVED

Related Links

• Role of the vein of Marshall in atrial fibrillation recurrences after catheter ablation: therapeutic effect of ethanol infusion.

MeSH Terms

Conditions

Tachycardia, Ventricular; Atrial Fibrillation

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Results Point of Contact

• Title: Miguel Valderrabano, MD
• Organization: Houston Methodist Hospital, Dept of Cardiology

MValderrabano@houstonmethodist.org

713 441 5231

Study Officials

• Miguel Valderrabano, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients will be blinded to the randomization outcome
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects who meet inclusion criteria will be randomized to either a conventional PVAI or PVAI with VOM procedure.

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: July 12, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 21, 2025
• Results First Posted: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)