Phase 3
Completed N=104
Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis
Acute Alcoholic Hepatitis
Source: ClinicalTrials.gov NCT01809132 ↗
Enrolled (actual)
104
Serious AEs
61.2%
Results posted
Dec 2020
Primary outcomePrimary: 180 Days Mortality — 17; 22; 0 Participants — p=.30
◆ Published Evidence
Highly cited
102citations · ~26 / year
IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis.
Summary
This study will compare two different treatments of acute alcoholic hepatitis. The current standard of care is treatment with corticosteroids (methylprednisolone). This will be compared to treatment with anakinra, pentoxifylline, plus zinc sulfate. The participants will be treated and followed for 6 months and the two treatment groups will be compared for differences in death rates and laboratory tests that measure liver and gut function.
Linked Publications (4)
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IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis.
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Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis.
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Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice.
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Safety, Pharmacokinetics, and Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-Associated Hepatitis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 180 Days Mortality |
17; 22; 0 | .30 |
| SECONDARY MELD Score at 28 Days |
22.57; 20.95 | .42 |
| SECONDARY MELD Score at 90 Days |
15.50; 16.38 | .75 |
| SECONDARY MELD Score at 180 Days |
15.81; 11.85 | .17 |
Eligibility Criteria
Inclusion Criteria
- Ability to provide informed consent by subject or appropriate family member
- Age between 21-70 years
- Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment
- d. At least 2 of the following symptoms of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain
- Liver biopsy showing alcoholic hepatitis (steatohepatitis) OR ultrasound of liver showing increased echogenicity OR CT scan showing decreased attenuation of liver compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1 weighted images) If liver biopsy confirms diagnosis of alcoholic hepatitis then requirement for AST elevation > 50 is waived. The liver biopsy must be done within 60 days of study enrollment.
- AST levels:
- AST> Or equal to 50 IU/mL but less than 500 IU/mL
- AST> ALT, ratio AST/ALT> 1.5; ALT 38°C and positive blood or ascites cultures and on appropriate antibiotic therapy for ≥ 3 days within 3 days of inclusion
- Acute gastrointestinal bleeding requiring >2 units blood transfusion within the previous 4 days
- Undue risk from immunosuppression: Positive HBsAg; a positive skin PPD skin test, a positive quantiferon, or history of treatment for tuberculosis; history of any malignancy except skin cancer but including hepatocellular carcinoma within the last five years; HIV infection
- Recent previous treatment with corticosteroids or other immunosuppressive medications including specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors within the previous 3 months. Treatment with corticosteroids for ≤3 days prior to baseline is acceptable.
- Evidence of acute pancreatitis: CT evidence or amylase or lipase > 5 X upper limit of normal (ULN).
- Serious cardiac, respiratory or neurologic disease or evidence of other liver diseases such as autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, hemochromatosis, secondary iron overload due to chronic hemolysis, alpha-1-antitrypsin deficiency
- Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl.
Data sourced from ClinicalTrials.gov (NCT01809132) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.