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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
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.
Yale New Haven Hospital, Yale School of Medicine
New Haven, Connecticut, United States
Change in biomarkers of inflammation
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 .
Time frame: day 3
Practicality of daily digoxin measurements
Time to 90% of patients have digoxin checked levels within the pre-specified time window
Time frame: Up to 28 days
Feasibility of digoxin dosing in a timely manner.
Time to 90% of patients receive every scheduled dose of the drug
Time frame: Up to 28 days
Feasibility of digoxin dose adjustments in renal insufficiency.
90% of necessary dose adjustments were made appropriately in response to digoxin levels
Time frame: Up to 28 days
Mortality at 7, 14, 28, 90 days. All cause mortality of patients enrolled in the trial.
The mortality rates at different time points in the digoxin group and in the control group
Time frame: Up to 90 days
Development of ECG abnormalities
The number and proportion of patients in the digoxin and control groups with ECG changes compared to baseline
Time frame: Up to 28 days
Recruitment
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?
Time frame: up to 90 days
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