Digoxin In Treatment of Alcohol Associated Hepatitis (DIGIT-AlcHep)

October 7, 2025 updated by: Bubu Banini, MD, PhD, Yale University

Digoxin In Treatment of Alcohol Associated Hepatitis (DIGIT-AlcHep)

Prospective, single center, open label, randomized controlled trial to explore whether digoxin treatment affects cytokine levels as biomarkers of inflammation in patients with acute alcohol associated hepatitis, digoxin administration and dose adjustment.

The study intervention will be intravenous digoxin (renal-based dosing for maximum of 28 days) versus no digoxin in an open-label 1:1 randomized allocation of patients with severe acute alcohol associated hepatitis.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Severe alcohol associated hepatitis is a condition of acute on chronic immune liver dysfunction that is associated with high mortality, necessitating a search for drugs that may prove safe and efficacious in treating this disease. Pre-clinical studies suggest that digoxin, which is currently used for treating cardiac conditions, is also effective in improving alcohol-associated liver injury. To date, there have been no clinical studies of digoxin use in patients with alcohol associated hepatitis.

The primary objective of this randomized control study of digoxin versus no digoxin in patients with severe alcohol associated hepatitis is to explore whether digoxin treatment affects cytokine levels as biomarkers of inflammation in patients hospitalized with severe alcohol associated hepatitis.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital, Yale School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

1. Diagnosis of alcohol associated hepatitis based on clinical criteria or histologic evidence

  1. Clinical criteria:

    • Onset of jaundice (bilirubin >3 mg/dL) within the prior 8 weeks
    • Regular alcohol use > 6 months, with intake of > 40 g/day (>280 g/week) for women; and > 60 g/day (>420 g/week) for men
    • AST > 50 IU/l
    • AST: ALT > 1.5 and both values < 400 IU/l

  2. Histological evidence of alcohol associated hepatitis*

    2. MDF >32 or MELD ≥ 20 to ≤ 35 on Day 0 of the trial

    3. Age between 21 and 70 years, inclusive

    * In patients with possible alcohol associated hepatitis with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use, or atypical/abnormal laboratory tests (e.g., AST < 50 IU/IU/L or > 400 IU/IU/L, AST/ALT ratio < 1.5), antinuclearantibody > 1:160 or SMA > 1:80, standard of care liver biopsy may be performed as per discretion of the primary attending physician to confirm alcohol associated hepatitis and exclude competing etiologies. The decision to perform liver biopsy will be made by the primary team and will occur regardless of the study. As per current SOC, a liver biopsy may be obtained to confirm suspected alcohol-associated hepatitis and to rule out other potential etiologies of liver disease.

    If a liver biopsy is performed for clinically indicated reasons, we will store liver tissue that is left over after the portion needed for the primary indication has been identified.

    Exclusion Criteria:

    1. - Currently pregnant or breastfeeding
    2. - Inability of patient, legally authorized representative or next-of-kin to provide informed consent
    3. - Allergy or intolerance to digoxin
    4. - Clinically active C. diff infection
    5. - Positive test for COVID-19 within 14 days prior to the screening visit
    6. - Acute hepatitis E, Cytomegalovirus, Epstein Barr Virus, Herpes Simplex Virus

    7- History of other liver diseases including hepatitis B (positive HBsAg or HBV DNA), hepatitis 8-C (positive HCV RNA), autoimmune hepatitis, Wilson disease, genetic hemochromatosis, alpha1-antitrypsin deficiency.

    8-Diagnosis of Drug Induced Liver Injury (DILI), or other etiologies seen on liver imaging.

    9 - History of HIV infection (positive HIV RNA or on treatment for HIV infection)

    10 - Current diagnosis of cancer

    11- Renal failure defined by GFR <30 mL/min

    12 - Refractory ascites, defined as having more than 4 paracenteses in the preceding 8 weeks despite diuretic therapy

    13 - Prior exposure to experimental therapies or other clinical trial in last 3 months

    14 - Current acute or chronic pancreatitis

    15 - Active gastrointestinal bleeding unless resolved for >48 hours

    16 - Experiencing withdrawal seizures or considered at high risk for alcohol withdrawal seizures or delirium tremens

    17 - Heart rate less than 60 bpm at screening visit or at baseline

    18 - Current diagnosis of atrial fibrillation

    19 - Cardiomyopathy

    20 - Heart failure

    21 - Severe aortic valve disease

    22 - Presence of Accessory arterio-ventricular pathway (eg Wolf-Parkinson-White syndrome)

    23 - Complete heart block or second degree arterio-ventricular block without pacemaker or implantable cardiac device

    24 - Any of the following within the previous 6 months: myocardial infarction, percutaneous intervention, pacemaker/implantable cardiac device implantation, cardiac surgery or stroke

    25 - Current use of the following medications:

    • Antiarrhythmic (amiodarone, dofetilide, sotalol, dronedarone)
    • Parathyroid hormone analog (teriparatide)
    • Thyroid supplement (thyroid, levothyroxine sodium)
    • Sympathomimetics or ionotropic drugs (epinephrine, norepinephrine, dopamine, dobutamine, milrinone)
    • Neuromuscular blocking agents (succinylcholine)
    • Calcium supplement
    • Ivabradine
    • Disulfiram

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Digoxin
In the digoxin arm, the intervention to be administered will be intravenous digoxin dosed by weight and by renal function using an adaption of the established FDA nomogram. Participants randomized to digoxin will receive an intravenous digoxin loading dose administered in 3 doses over 24 hours starting on Day 1. Digoxin levels will be monitored daily throughout the participant's hospital stay, to a maximum of 28 days. Digoxin will be discontinued at the time discharge if before 28 days.
Drug: Intravenous digoxin

Loading dose: the total loading dose of digoxin will be determined using the Loading nomogram. The FDA-recommended total IV digoxin loading dose range is 8 to 12 mcg/kg. The lowest recommended dose of 8 mcg/kg was used in constructing the digoxin Loading nomogram that will be used in this trial.

Maintenance dose: the maintenance dose will be started approximately 24 hours after initiation of digoxin loading. The post-loading digoxin trough will be reviewed prior to starting maintenance dosing.

Subjects on P-gp inhibitors or spironolactone, will have an additional digoxin level performed 12-hours after any dose adjustment. Once digoxin levels are stable, 24-hour blood draws will be performed.

Other Names:
  • Lanoxin
No Intervention: Arm B: No Digoxin
In the no digoxin arm, no study drug or placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in biomarkers of inflammation
Time Frame: day 3
Change in biomarkers of inflammation cytokine levels (pg/mL) in participants with acute alcohol associated hepatitis treated with digoxin versus no digoxin at day 3 of the study .
day 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of digoxin dose adjustments in renal insufficiency.
Time Frame: Up to 28 days
90% of necessary dose adjustments were made appropriately in response to digoxin levels
Up to 28 days
Development of ECG abnormalities
Time Frame: Up to 28 days
The number and proportion of patients in the digoxin and control groups with ECG changes compared to baseline
Up to 28 days
Practicality of daily digoxin measurements
Time Frame: Up to 28 days
Time to 90% of patients have digoxin checked levels within the pre-specified time window
Up to 28 days
Feasibility of digoxin dosing in a timely manner.
Time Frame: Up to 28 days
Time to 90% of patients receive every scheduled dose of the drug
Up to 28 days
Mortality at 7, 14, 28, 90 days. All cause mortality of patients enrolled in the trial.
Time Frame: Up to 90 days
The mortality rates at different time points in the digoxin group and in the control group
Up to 90 days
Recruitment
Time Frame: up to 90 days
Ability to recruit 4 patients per month IS THIS A YES/NO or can we present it as the mean number of participants recruited per month?
up to 90 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Organ dysfunction (Liver - Lille Score)
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of Lille score. The model is based on: Age, Albumin, Bilirubin (initial), Bilirubin (day 7), Creatinine, PT. Survival probability at 6 months is defined by a cutoff of 0.45: 6-month survival probability of patients with a Lille model above 0.45 is about 25% contrary to patients with a Lille model below this cutoff (85% survival).
Up to 28 days
Organ dysfunction (Liver) with Model for End-stage Liver Disease (MELD)
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of Model for End-stage Liver Disease (MELD) score, a number that ranges from 6 (least sick) to 40 (most sick) based on blood tests. The lab tests used to determine the MELD score are creatinine, bilirubin, sodium and international normalized ratio (INR).
Up to 28 days
Organ dysfunction (Liver Enzyme: Bilirubin)
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of the liver enzyme bilirubin
Up to 28 days
Organ dysfunction (Liver Enzyme: Alkaline Phosphatase [ALP])
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of liver enzymes (alkaline phosphatase [ALP])
Up to 28 days
Organ dysfunction (Liver Enzyme: Aspartate Aminotransferase [AST])
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of liver enzymes (aspartate aminotransferase [AST])
Up to 28 days
Organ dysfunction (Liver Enzyme: Alanine Aminotransferase [ALT])
Time Frame: Up to 28 days
Changes in liver-related function will be determined through assessment of liver enzymes (alanine aminotransferase [ALT])
Up to 28 days
Organ Dysfunction (Multi-Organ) with Sequential Organ Failure Assessment (SOFA)
Time Frame: Up to 28 days
Dysfunction in other organs will be assessed using Sequential Organ Failure Assessment (SOFA) score which is calculated based on a person's liver function, kidney function, nervous system, coagulation, circulation, and respiratory status. The score ranges from 0 (least sick) to 24 (most sick).
Up to 28 days
Organ Dysfunction (Multi-Organ) with the Multi-Organ Dysfunction Score (MODS)
Time Frame: Up to 28 days
Dysfunction in other organs will be assessed using Multi-organ dysfunction score (MODS), calculated based on a person's liver function, kidney function, nervous system, coagulation, circulation, and respiratory status. The score ranges from 0 (least sick) to 24 (most sick).
Up to 28 days
Development of new or recurrent renal failure.
Time Frame: Up to 28 days
Creatinine rise ≥ 0.5 mg/dL or ≥ 20% from baseline or requiring renal replacement therapy.
Up to 28 days
Racial and ethnic diversity in subject recruitment and retention.
Time Frame: Up to 90 days
Race and ethnicity of enrolled subjects and subjects who completed the study will be summarized using count and proportion to assess the study's objective of enrolling and retaining at least 10% Black and at least 10% Hispanic participants to study completion (90-days follow-up)follow-up.
Up to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Investigators

  • Principal Investigator: Bubu Banini, MD, PhD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2021

Primary Completion (Actual)

June 22, 2025

Study Completion (Actual)

September 12, 2025

Study Registration Dates

First Submitted

July 20, 2021

First Submitted That Met QC Criteria

August 12, 2021

First Posted (Actual)

August 20, 2021

Study Record Updates

Last Update Posted (Estimated)

October 9, 2025

Last Update Submitted That Met QC Criteria

October 7, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000030659

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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