Clinical Trial: Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis in Addition to Prednisolon Therapy
Brief 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 Summary:
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.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Early reduction in serum bilirubin level [ Time Frame: 7 days after randomisation ]
- Surrogate markers of liver function [ Time Frame: 7 days to 12 months ]Improvement of surrogate markers of cholesterol synthesis and liver synthesis capacity, e.g., lathosterol, cholestenol and desmosterol
Original Secondary Outcome: Same as current
Information By: Helsinki University
Dates:
Date Received: December 22, 2014
Date Started: April 2015
Date Completion:
Last Updated: January 18, 2017
Last Verified: January 2017
