Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis

Completed · Phase 2 · Has a placebo group

Conditions studied: Alcoholic Hepatitis

In brief

This multicenter, randomized, double blinded, placebo-controlled clinical trial is focused on novel treatments for severe alcoholic hepatitis (AH), a life-threatening stage of alcoholic liver injury that has a short-term mortality rate much higher than that of other liver diseases. The primary objective of the study is to determine the clinical efficacy and safety of Anakinra (plus zinc) compared to the current standard medical treatment consisting of prednisone in participants with clinically severe AH. Key secondary objectives broadly are as follows: (a) to evaluate the use of biomarkers to assess disease severity and treatment response; and (b) to develop novel endpoints to overcome the limitations of current assessment strategies for severe AH.

Key facts

Study ID

NCT04072822

Run by

Indiana University

People needed

147

Starts

2020-07-10

Expected to finish

2022-08-12

Last updated by the study team

2025-02-10

Who can join

Age: 21 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• AH, as defined by the NIAAA pan-consortia for AH:
• Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8 weeks to screening visit
• Regular consumption of alcohol with an intake of > 40 gm daily or >280gm weekly on average for women and > 60 gm daily or >420gm weekly on average for men for 6 months or more, with less than 8 weeks of abstinence before onset of jaundice
• AST > 50 IU/l
• AST:ALT > 1.5 and both values < 400 IU/l
• and/or histological evidence of AH*
• MELD 20-35 on day of randomization.
• Ages >21
• In patients with possible AH or AH with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g., patient denies excessive alcohol use), and atypical/abnormal laboratory tests (e.g., AST < 50 IU/L or > 400 IU/L, AST/ALT ratio < 1.5), antinuclear antibody > 1:160 or SMA > 1:80, a standard of care liver biopsy may be performed during current hospital admission to confirm AH and exclude competing etiologies

You may not qualify if…

• MELD SCORE <20 or > 35
• Active sepsis (positive blood or ascitic cultures) with Systemic Inflammatory Response Syndrome (SIRS) or hemodynamic compromise requiring intravenous pressors to maintain tissue perfusion
• Pneumonia as evidenced by radiological exam
• Multi-organ failure
• Renal failure defined by GFR <35 mL/min by CKD-EPI.
• Clinically active C. diff infection
• History of imaging of the liver (ultrasound, computerized tomography or magnetic resonance) showing other causes of jaundice
• 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 or strong suspicion of Drug Induced Liver Injury (DILI). Previously treated hepatitis C that was cured (sustained virological response with negative RNA ≥24 weeks following treatment) is not an exclusion.
• History of HIV infection (positive HIV RNA or on treatment for HIV infection)
• History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer
• History of other significant medical problems such as autoimmune diseases, severe asthma, psoriasis, Inflammatory Bowel Disease (IBD), etc. that might require immunosuppressive treatments
• Pregnancy or breastfeeding
• Prior exposure to experimental therapies in last 3 months
• Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 4 days within previous 30 days
• Need for inotropic pressor support to maintain perfusion to critical organs within prior 48 hours before randomization and initiation of experimental treatment
• Clinically significant pancreatitis- abdominal pain, elevated lipase (> 3 X ULN) and at least edema of pancreas with fat-stranding on CT scan
• Total WBC count > 30,000/mm3
• Known allergy or intolerance to therapeutic agents to be tested
• Inability to voluntarily obtain informed consent from participant or guardian
• Perceived inability to follow study procedures and comply with protocol
• Platelet count < 40,000 k/cumm.
• Positive PCR test for COVID -19 within 7 days prior to the baseline day 0 visit
• Active gastrointestinal bleeding defined as hematemesis or melena with a decrease in hemoglobin more than 2 g/dl in 24 hrs. Due to gastrointestinal bleeding, or with a decrease in mean arterial BP to < 65 mmHg.
• Positive test is exclusionary only during screening period. If a patient tests positive any time after baseline randomization, a positive PCR test for COVID-19 will be considered as a SAE.

Where it is running

• Mayo Clinic — Phoenix, Arizona, United States
• Mayo Clinic — Jacksonville, Florida, United States
• Indiana Universtiy — Indianapolis, Indiana, United States
• University of Louisville — Louisville, Kentucky, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States
• University of Texas Southwestern Medical School — Dallas, Texas, United States
• Virginia Commonwealth University — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.