Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis

• Status: Completed
• Trial end date: 2018-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mack Mitchell
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); The Cleveland Clinic; University of Louisville; University of Massachusetts, Worcester
• Treatments: Interleukin 1 Receptor Antagonist Protein; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Pentoxifylline; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Zinc; Zinc Sulfate

Criteria

Inclusion Criteria:

1. Ability to provide informed consent by subject or appropriate family member

2. Age between 21-70 years

3. Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment

4. d. At least 2 of the following symptoms of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain

5. 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.

6. AST levels:

• AST> Or equal to 50 IU/mL but less than 500 IU/mL

• AST> ALT, ratio AST/ALT> 1.5; ALT < 200 IU/mL

• or biopsy proven alcoholic hepatitis.

7. Model for End-Stage Liver Disease (MELD) ≥ 20 and Maddrey DF ≥ 32.

8. Willingness to utilize two reliable forms of contraception (both males and females of childbearing potential) from screening through the first 6 weeks of the study.

Exclusion Criteria:

1. Hypotension with BP < 80/50 after volume repletion

2. Pregnancy; incarceration; inability to provide consent or lack of appropriate family member

3. Signs of uncontrolled systemic infection: Fever > 38°C and positive blood or ascites cultures and on appropriate antibiotic therapy for ≥ 3 days within 3 days of inclusion

4. Acute gastrointestinal bleeding requiring >2 units blood transfusion within the previous 4 days

5. 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

6. 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.

7. Evidence of acute pancreatitis: CT evidence or amylase or lipase > 5 X upper limit of normal (ULN).

8. 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

9. Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl.