Digoxin In Treatment of Alcohol Associated Hepatitis

Launched by YALE UNIVERSITY · Aug 12, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating whether a medication called digoxin can help reduce inflammation in patients with severe acute alcoholic hepatitis, which is a serious liver condition caused by heavy drinking. The study will compare patients receiving intravenous digoxin for up to 28 days to those who do not receive the drug. Researchers are particularly interested in how digoxin affects certain substances in the body that indicate inflammation.

To participate in this trial, individuals must be between the ages of 21 and 70 and have a diagnosis of alcoholic hepatitis confirmed by specific health criteria. They should have experienced symptoms like jaundice (yellowing of the skin) and have been regular drinkers for at least six months. However, there are several health conditions and factors that could exclude someone from participating, such as pregnancy, certain heart conditions, or recent serious infections. Participants will receive regular health assessments, and the study team will closely monitor their condition throughout the trial.

Gender

ALL

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