Using digoxin to treat acute alcohol associated hepatitis

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

This study is testing if digoxin can help reduce inflammation in people with severe alcohol-related hepatitis to see if it improves their chances of recovery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Yale University (other)
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05014087 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-center, open-label, randomized controlled trial aimed at evaluating the effects of digoxin on cytokine levels in patients with severe acute alcohol associated hepatitis. Participants will receive intravenous digoxin for up to 28 days, with a focus on assessing its impact on inflammation biomarkers compared to a control group receiving no digoxin. The study seeks to address the high mortality associated with this condition by exploring a potential new treatment option. The trial will include patients diagnosed with alcohol associated hepatitis based on clinical or histological criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 70 with a diagnosis of severe acute alcohol associated hepatitis and specific clinical criteria.

Not a fit: Patients with mild liver disease or those with confounding factors affecting the diagnosis of alcohol associated hepatitis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from severe alcohol associated hepatitis.

How similar studies have performed: While pre-clinical studies suggest potential benefits of digoxin for liver injury, there have been no prior clinical studies specifically investigating its use in alcohol associated hepatitis.

Eligibility criteria

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

Where this trial is running

New Haven, Connecticut

• Yale New Haven Hospital, Yale School of Medicine — New Haven, Connecticut, United States (RECRUITING)

Study contacts

• Principal investigator: Bubu Banini, MD, PhD — Yale University
• Study coordinator: Bubu Banini, MD, PhD

Conditions: Acute Alcoholic Hepatitis, Chemical and Drug Induced Liver Injury, Alcohol-Induced Disorders, Steatohepatitis Caused by Ingestible Alcohol, Acute alcoholic hepatitis, Liver injury, Liver inflammation, Liver disease