Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis
Condition: Acute Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Detailed description: 
      This study will test the hypothesis that the syndrome of acute alcoholic hepatitis results
      from severe inflammation and dysregulated cytokines. Steroid monotherapy is not effective in
      all patients and this study will utilize compounds that have the potential to improve gut
      barrier function, to reduce the associated inflammation, and to prevent the development of
      hepatorenal syndrome and other organ failure.

      Patients will be randomized to receive 28 days of methylprednisolone 32 mg daily OR therapy
      that includes a combination of anakinra (interleukin-1 receptor antagonist) 100mg by
      subcutaneous injection daily for 14 days plus pentoxifylline 400 mg orally three times daily
      for one month plus zinc supplements (220 mg of zinc sulfate) given orally for 6 months. This
      combination strategy will address the acute inflammatory component of the disease (anakinra)
      and protect against development of hepatorenal syndrome (pentoxifylline), one of the most
      frequent causes of death in severe acute alcoholic hepatitis, and improve gut mucosal
      integrity (zinc supplements). The primary outcome will be 6 month mortality rate. Secondary
      outcomes will be measured at 30, 90 and 180 days.

      Individuals who are not participating in the interventional arm of the trial will be receive
      standard care and be observed for 6 months. They will be enrolled to have baseline and
      interval health information and laboratory results collected.
    

Intervention name(s): Anakinra; Pentoxifylline; Zinc Sulfate; Methylprednisolone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection.; Pentoxifylline, generic; Zinc Sulfate, nutritional supplement; Methylprednisolone, corticosteroid
Other intervention name(s): Kineret; Pentoxifylline, generic; Zinc Sulfate, generic; Methylprednisolone, generic
Intervention MeSH terms: Zinc; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Interleukin 1 Receptor Antagonist Protein; Pentoxifylline; Zinc Sulfate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Hepatitis, alcoholic; pentoxifylline; zinc; anakinra; glucocorticoids; MELD score; Intestinal mucosa