Overview

Prospective, single center, open label, randomized controlled trial to determine the feasibility of conducting a future study with respect to patient recruitment, 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.

Eligibility

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
   3. MDF >32 or MELD ≥ 20 to ≤ 35 on Day 0 of the trial
   4. Age between 21 and 70 years, inclusive

      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