Alcoholic Hepatitis Clinical Trial
Official title:
Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis in Addition to Prednisolon Therapy
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.
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
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