60 Participants Needed

Digoxin for Alcoholic Hepatitis

(DIGIT-AlcHep Trial)

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CD
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Overseen ByCamalene Chrysostoum
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including antiarrhythmics, parathyroid hormone analogs, thyroid supplements, sympathomimetics or ionotropic drugs, neuromuscular blocking agents, calcium supplements, ivabradine, and disulfiram.

Is digoxin generally safe for humans?

Digoxin has been used for many years, but it can be toxic if not dosed correctly, especially in people with liver or kidney problems. Women and older adults may be at higher risk for digoxin toxicity, which can lead to serious health issues. However, modern treatments can effectively manage toxicity if it occurs.12345

How does the drug digoxin differ from other treatments for alcoholic hepatitis?

Digoxin is unique because it targets a specific pathway (PKM2-HIF-1α) involved in liver inflammation and damage, which is different from other treatments for alcoholic hepatitis. It has been shown to reduce liver damage and inflammation in animal models, suggesting a novel approach compared to existing therapies.26789

Research Team

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Bubu Banini, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

Adults aged 21-70 with severe acute alcohol-associated hepatitis can join this trial. They must have a history of regular heavy drinking and specific blood test results indicating liver damage. Excluded are pregnant or breastfeeding individuals, those allergic to digoxin, with certain infections including COVID-19, other liver diseases, HIV, cancer, serious heart conditions or on conflicting medications.

Inclusion Criteria

- AST > 50 IU/l
- AST: ALT > 1.5 and both values < 400 IU/l
I am between 21 and 70 years old.
See 7 more

Exclusion Criteria

Heart rate less than 60 bpm at screening visit or at baseline
I am currently taking specific medications.
I am not taking any specific heart rhythm medications.
See 30 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous digoxin dosed by weight and renal function for a maximum of 28 days

Up to 28 days
Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

Treatment Details

Interventions

  • Digoxin
Trial OverviewThe study is testing if intravenous digoxin is safe and effective for treating severe acute alcoholic hepatitis compared to no treatment. Participants will be randomly assigned to receive either digoxin (with doses adjusted based on kidney function) or no digoxin in an open-label format for up to 28 days.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: DigoxinExperimental Treatment1 Intervention
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.
Group II: Arm B: No DigoxinActive Control1 Intervention
In the no digoxin arm, no study drug or placebo will be administered.

Digoxin is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Lanoxin for:
  • Atrial fibrillation
  • Atrial flutter
  • Supraventricular tachycardia
  • Congestive heart failure
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Approved in United States as Lanoxin for:
  • Atrial fibrillation
  • Atrial flutter
  • Supraventricular tachycardia
  • Congestive heart failure
🇨🇦
Approved in Canada as Lanoxin for:
  • Atrial fibrillation
  • Atrial flutter
  • Supraventricular tachycardia
  • Congestive heart failure
🇯🇵
Approved in Japan as Lanoxin for:
  • Atrial fibrillation
  • Atrial flutter
  • Supraventricular tachycardia
  • Congestive heart failure

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

Findings from Research

The incidence of digoxin toxicity has significantly declined due to a lower therapeutic range, better drug therapies for heart failure, and improved dosing methods, making it less common and less fatal than in the past.
Modern treatments, such as the emergency use of antidigoxin Fab fragments, allow for quick and effective management of digoxin toxicity, and there is potential to use these treatments for non-life-threatening cases to enhance patient comfort and reduce costs.
Mechanisms, manifestations, and management of digoxin toxicity in the modern era.Bauman, JL., Didomenico, RJ., Galanter, WL.[2018]
In a study involving 24 participants (12 with cirrhosis and 12 healthy volunteers), patients with cirrhosis showed significantly higher serum levels of metildigoxin compared to healthy individuals, indicating altered drug metabolism due to liver impairment.
The research suggests that patients with cirrhosis are at a greater risk of digitalis toxicity when treated with standard doses of metildigoxin, as their liver function affects the drug's clearance and distribution, unlike beta-acetyldigoxin which did not show significant differences.
Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin.Rameis, H., Woodcock, B., Bonelli, J., et al.[2013]
A study of 727 patients from 2000 to 2020 revealed that digoxin toxicity remains a significant public health concern, with a 12.7% in-hospital mortality rate and 42.7% mortality at one year after admission.
Patients treated with digoxin immune fab (DIF) had more severe health issues, but showed nonsignificant trends toward lower in-hospital mortality and reduced early readmissions compared to a matched cohort, indicating potential benefits of DIF in high-acuity cases.
Characteristics and Outcomes of Suspected Digoxin Toxicity and Immune Fab Treatment Over the Past Two Decades-2000-2020.Peters, AE., Chiswell, K., Hofmann, P., et al.[2022]

References

Mechanisms, manifestations, and management of digoxin toxicity in the modern era. [2018]
Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin. [2013]
Characteristics and Outcomes of Suspected Digoxin Toxicity and Immune Fab Treatment Over the Past Two Decades-2000-2020. [2022]
Age- and gender-specific incidence of hospitalisation for digoxin intoxication. [2018]
Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality. [2022]
Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. [2020]
New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. [2023]
The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. [2019]
[Pharmacokinetics of beta-methyldigoxin and beta-acetyldigoxin in patients with cirrhosis of the liver (author's transl)]. [2013]