알코올 관련 간염의 치료에서 디곡신 (DIGIT-AlcHep)

In the digoxin arm, the intervention to be administered will be intravenous digoxin dosed by weight and by renal function using an adaption of the established FDA nomogram. Participants randomized to digoxin will receive an intravenous digoxin loading dose administered in 3 doses over 24 hours starting on Day 1. Digoxin levels will be monitored daily throughout the participant's hospital stay, to a maximum of 28 days. Digoxin will be discontinued at the time discharge if before 28 days.

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.

• 라녹신

In the no digoxin arm, no study drug or placebo will be administered.

Change in IL-6, IL-10 and TNF-alpha levels (pg/ml) at day 3 in participants with acute alcohol associated hepatitis treated with digoxin vs no digoxin.

Practicality of daily digoxin measurements is recorded at the participant level as the proportion of timepoints where serum digoxin levels are checked within the pre-specified time window. It is summarized and reported as the mean and standard deviation of the proportion of eligible timepoints.

Feasibility of digoxin dosing is recorded at the participant level as the proportion of eligible timepoints where the scheduled digoxin dose was given. It is summarized and reported as the mean and standard deviation of the proportion of scheduled timepoints.

Feasibility of digoxin dose adjustments in renal insufficiency is recorded at the participant level as the proportion of timepoints where necessary dose adjustments were made appropriately in response to digoxin levels. Renal insufficiency was defined as a creatinine rise ≥ 0.3 mg/dL over 48 hours or ≥ 20% from baseline or requiring renal replacement therapy. It is reported as the mean and standard deviation of the proportion of timepoints.

The mortality rates at different time points

It refers to any type of arrhythmia which represents a change from baseline. It is reported as the proportion of individuals who developed an arrhythmia.

Ability to recruit 4 patients per month to reach anticipated enrollment of 60. Data presented here is the number participants enrolled.

Changes in liver-related function will be determined through assessment of Lille score. The model is based on: Age, Albumin, Bilirubin (initial), Bilirubin (day 7), Creatinine, PT. Survival probability at 6 months is defined by a cutoff of 0.45: 6-month survival probability of patients with a Lille model above 0.45 is about 25% contrary to patients with a Lille model below this cutoff (85% survival).

Changes in liver-related function will be determined through assessment of Model for End-stage Liver Disease (MELD) score, a number that ranges from 6 (least sick) to 40 (most sick) based on blood tests. The lab tests used to determine the MELD score are creatinine, bilirubin, sodium and international normalized ratio (INR).

Changes in liver-related function will be determined through assessment of the liver enzyme bilirubin

Changes in liver-related function will be determined through assessment of liver enzymes (alkaline phosphatase [ALP])

Changes in liver-related function will be determined through assessment of liver enzymes (aspartate aminotransferase [AST])

Changes in liver-related function will be determined through assessment of liver enzymes (alanine aminotransferase [ALT])

Dysfunction in other organs will be assessed using Sequential Organ Failure Assessment (SOFA) score which is calculated based on a person's liver function, kidney function, nervous system, coagulation, circulation, and respiratory status. The score ranges from 0 (least sick) to 24 (most sick).

Dysfunction in other organs will be assessed using Multi-organ dysfunction score (MODS), calculated based on a person's liver function, kidney function, nervous system, coagulation, circulation, and respiratory status. The score ranges from 0 (least sick) to 24 (most sick).

Creatinine rise ≥ 0.5 mg/dL or ≥ 20% from baseline or requiring renal replacement therapy.

Race and ethnicity of enrolled subjects and subjects who completed the study will be summarized using count and proportion to assess the study's objective of enrolling and retaining at least 10% Black and at least 10% Hispanic participants to study completion (90-days follow-up)follow-up.