Status:
COMPLETED
Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis
Lead Sponsor:
Mack Mitchell
Collaborating Sponsors:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Cleveland Clinic
Conditions:
Acute Alcoholic Hepatitis
Eligibility:
All Genders
21-70 years
Phase:
PHASE2
PHASE3
Brief 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 w...
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...
Eligibility Criteria
Inclusion
- 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 \< 200 IU/mL
- or biopsy proven alcoholic hepatitis.
- Model for End-Stage Liver Disease (MELD) ≥ 20 and Maddrey DF ≥ 32.
- 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
- Hypotension with BP \< 80/50 after volume repletion
- Pregnancy; incarceration; inability to provide consent or lack of appropriate family member
- 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
- 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.
Key Trial Info
Start Date :
September 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 1 2018
Estimated Enrollment :
104 Patients enrolled
Trial Details
Trial ID
NCT01809132
Start Date
September 1 2013
End Date
October 1 2018
Last Update
November 1 2021
Active Locations (4)
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1
University of Louisville
Louisville, Kentucky, United States, 40202
2
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
3
Cleveland Clinic
Cleveland, Ohio, United States, 44195
4
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9030