Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
Primary Purpose
Alcoholic Hepatitis, Alcoholic Cirrhosis
Status
Completed
Phase
Early Phase 1
Locations
Finland
Study Type
Interventional
Intervention
Ciprofloxacin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholic Hepatitis focused on measuring alcoholic, hepatitis, cirrhosis, cholesterol metabolites, ciprofloxacin
Eligibility Criteria
Inclusion Criteria:
Severe alcoholic hepatitis; Maddrey above 300
Exclusion Criteria:
Viral hepatitis Remarkable bleeding in the gastrointestinal tract Serious bacterial infection Hepatorenal syndrome Earlier participation in this study Malignant disease not in remission Other liver disease affecting remarkably the outcome of alcoholic liver disease Mental retardation
Sites / Locations
- University Hospital of Helsinki
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Ciprofloxacin
Placebo
Arm Description
Oral administration of Ciprofloxacin 500mg twice daily
Oral administration of Placebo pill twice daily
Outcomes
Primary Outcome Measures
Death at 28 days
Death at 3 months
Death at 6 months
Secondary Outcome Measures
Early reduction in serum bilirubin level
Surrogate markers of liver function
Improvement of surrogate markers of cholesterol synthesis and liver synthesis capacity, e.g., lathosterol, cholestenol and desmosterol
Full Information
NCT ID
NCT02326103
First Posted
December 22, 2014
Last Updated
January 18, 2017
Sponsor
University of Helsinki
1. Study Identification
Unique Protocol Identification Number
NCT02326103
Brief Title
Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
Official Title
Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis in Addition to Prednisolon Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Helsinki
4. Oversight
Data Monitoring Committee
No
5. Study Description
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 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:
Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + ciprofloxacin 1000 mg/ day for 120 days or
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis, Alcoholic Cirrhosis
Keywords
alcoholic, hepatitis, cirrhosis, cholesterol metabolites, ciprofloxacin
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ciprofloxacin
Arm Type
Active Comparator
Arm Description
Oral administration of Ciprofloxacin 500mg twice daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral administration of Placebo pill twice daily
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Intervention Description
Comparison of ciprofloxacin with placebo in alcoholic hepatitis
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Death at 28 days
Time Frame
28 days after randomisation
Title
Death at 3 months
Time Frame
3 months after randomisation
Title
Death at 6 months
Time Frame
6 months after randomisation
Secondary Outcome Measure Information:
Title
Early reduction in serum bilirubin level
Time Frame
7 days after randomisation
Title
Surrogate markers of liver function
Description
Improvement of surrogate markers of cholesterol synthesis and liver synthesis capacity, e.g., lathosterol, cholestenol and desmosterol
Time Frame
7 days to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Severe alcoholic hepatitis; Maddrey above 300
Exclusion Criteria:
Viral hepatitis Remarkable bleeding in the gastrointestinal tract Serious bacterial infection Hepatorenal syndrome Earlier participation in this study Malignant disease not in remission Other liver disease affecting remarkably the outcome of alcoholic liver disease Mental retardation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Perttu Sahlman, MD
Organizational Affiliation
University Hospital of Helsinki
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Helsinki
City
Helsinki
ZIP/Postal Code
00029HUS
Country
Finland
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No IPD will be shared with other researchers during the study or during the analysis of the results.
Learn more about this trial
Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
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