Status:
COMPLETED
Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis
Lead Sponsor:
Indiana University
Collaborating Sponsors:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Conditions:
Alcoholic Hepatitis
Eligibility:
All Genders
21+ years
Phase:
PHASE2
Brief Summary
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 t...
Eligibility Criteria
Inclusion
- Inclusion Criteria
- 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
- Exclusion Criteria
- 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.
Exclusion
Key Trial Info
Start Date :
July 10 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 12 2022
Estimated Enrollment :
147 Patients enrolled
Trial Details
Trial ID
NCT04072822
Start Date
July 10 2020
End Date
August 12 2022
Last Update
February 10 2025
Active Locations (10)
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1
Mayo Clinic
Phoenix, Arizona, United States, 85054
2
Mayo Clinic
Jacksonville, Florida, United States, 32224
3
Indiana Universtiy
Indianapolis, Indiana, United States, 46202-2879
4
University of Louisville
Louisville, Kentucky, United States, 40292