Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
Condition: Alcoholic Hepatitis; Alcoholic Cirrhosis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic; Liver Cirrhosis, Alcoholic; Fibrosis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The study is aimed to evaluate the additional role of ciprofloxacin therapy in severe
      alcoholic hepatitis combined to prednisolone therapy in an open-label placebo controlled
      manner.
    

Detailed description: 
      Introduction: Alcoholic hepatitis (AH) is an inflammatory liver injury associated with
      longstanding excess alcohol consumption. Disease spectrum varies from asymptomatic
      transaminase elevations to fulminate liver failure. In hospital mortality in patients with
      severe alcoholic hepatitis not responding to corticosteroids is over 30 %.

      Alcohol increases gut permeability and promotes the translocation of lipopolysaccharide (LPS)
      from the gut lumen the portal vein, and further to Kupffer cells, where LPS binds to CD14,
      ultimately activating multiple cytokine genes.

      Diagnosis of AH is based on history of heavy alcohol use, symptoms like jaundice and on
      typical laboratory findings, and in uncertain cases on liver biopsy.

      Determination of the severity of alcoholic hepatitis is essential for assessment of the
      disease prognosis and selection therapy. Cessation of alcohol consumption is mandatory for
      further therapy. Several scoring systems are available to assess the severity and the
      prognosis of alcohol hepatitis. Maddrey discrimination function (DF) is most widely used and
      enables to identify patients with severe alcohol hepatitis responding to corticosteroid
      therapy.

      The first line therapy in severe alcoholic hepatitis (DF≥32) is prednisolone. However, those
      not responding to steroids have 77 % 6 months mortality.

      New treatment options for severe AH are desperately needed. Although increased bacterial and
      LPS translocation are considered to have central role in the pathogenesis of AH no controlled
      studies of antibiotics in alcoholic hepatitis has been published. In Finland 600 AH requiring
      hospitalization are diagnosed annually.

      Study objective: To evaluate to additional role of ciprofloxacin therapy in severe alcoholic
      hepatitis combined to prednisolone therapy.

      Moreover, we try to find new and better predictors for liver injury and treatment response.

      Patients: 150 AH patients, with Maddrey DF >32.

      Randomization: Patients with severe AH are randomized at hospitalization 1:1 to receive:

        1. Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + ciprofloxacin 1000
           mg/ day for 120 days or

        2. Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + placebo/ day for 120
           days Measurement of response Early change in bilirubin levels (ECBL= S-Bil(Day
           0)-S-Bil(Day7 )>0 Lille Score >0.45 day 7. Change in serum sterol levels as surrogate
           markers of cholesterol synthesis (reflecting liver function and severity of cholestasis)
           Primary end point Mortality at day 28, at 6 months and at 12 months Secondary end
           points: Proportion of patients with early change in bilirubin levels (ECBL= S-Bil(Day
           0)-S-Bil(Day7 )>0 Proportion of patients with Lille Score >0.45 day 7 Recovery of liver
           function parameters in 1 and 3 months
    

Intervention name(s): Ciprofloxacin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Comparison of ciprofloxacin with placebo in alcoholic hepatitis
Intervention MeSH terms: Ciprofloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: alcoholic; hepatitis; cirrhosis; cholesterol metabolites; ciprofloxacin