Digoxin In Treatment of Alcohol Associated Hepatitis

• Status: Not yet recruiting
• Trial end date: 2024-08-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Digoxin

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 to 60 or MELD 20 to 30 on Day 0 of the trial

3. Started on steroid treatment for acute alcohol associated hepatitis

4. Age between 21 and 65 years, inclusive

Exclusion Criteria:

• Currently pregnant or breastfeeding

• Inability of patient, legally authorized representative or next-of-kin to provide informed consent

• Allergy or intolerance to digoxin

• Clinically active C. diff infection

• Positive test for COVID-19 within 14 days prior to the screening visit

• Acute hepatitis E, Cytomegalovirus, Epstein Barr Virus, Herpes Simplex Virus

• History of other liver diseases including hepatitis B (positive HBsAg or HBV DNA), hepatitis C (positive HCV RNA), autoimmune hepatitis, Wilson disease, genetic hemochromatosis, alpha1-antitrypsin deficiency, strong suspicion for Drug Induced Liver Injury (DILI), or other etiologies seen on liver imaging

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

• Current diagnosis of cancer

• Renal failure defined by GFR <30 mL/min

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

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

• Current acute or chronic pancreatitis

• Active gastrointestinal bleeding unless resolved for >48 hours

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

• Heart rate less than 60 bpm at screening visit or at baseline

• Current diagnosis of atrial fibrillation

• Cardiomyopathy

• Heart failure

• Severe aortic valve disease

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

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

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

• Current use of the following medications: Antiarrthymics (amiodarone, dofetilide, sotalol, dronedarone), Parathyroid hormone analog (teriparatide), Thyroid supplement (thyroid), Sympathomimetics or ionotropic drugs (epinephrine, norepinephrine, dopamine, dobutamine, milrinone), Neuromuscular blocking agents (succinylcholine), Calcium supplement, Ivabradine, Disulfiram