Efficacy of Antibiotic Therapy in Severe Alcoholic Hepatitis Treated With Prednisolone
Condition: Alcoholic Hepatitis; Alcoholic Liver Disease
MeSH terms: Hepatitis A; Hepatitis; Liver Diseases; Hepatitis, Alcoholic; Liver Diseases, Alcoholic
Study type: Interventional
Phase: Phase 3

Summary: 
      Treatment of reference of severe alcoholic hepatitis is based on corticosteroids, given for
      28 days. However, about 25-35% of patients do not take benefit from this treatment and die
      within the 6 months following the diagnosis. Numerous trials have evaluated the impact of
      several strategies in association with corticosteroids. None of them has shown an improvement
      in survival (primary endpoint) as compared to corticosteroids alone.

      The project is based on an approach never tested in a randomized controlled trial in severe
      alcoholic hepatitis, targeting the group of patients at high risk of death (25-35% at 2
      months). This approach is based on animal and human studies.Antibiotics are effective in
      animal models and in other circumstances characterized by liver failure such as
      gastrointestinal bleeding related to portal hypertension. The interest of studying this
      population is emphasized by the frequency of infections in these critically ill patients.
      Antibiotics will be administered before the development of any infection, as it is likely
      that these patients present with mesenteric bacterial adenitis without systemic signs of
      infection. Primary endpoint will be 2-month survival as most deaths occur within 60 days and
      treatment is given for 30 days.
    

Detailed description: 
      This is a multicenter double-blind randomized controlled study on two parallel groups.

      Once inclusion and exclusion criteria verified and after having obtained patient written
      consent, participative centers will process to inclusion in the trial.

      Corticosteroids as well as antibiotics or their placebo will be started orally. Patients will
      be managed in the hospital unit until day 7, which corresponds to the evaluation of response
      to treatment using the Lille model. After this 7-day period, patients will be followed-up at
      day 14, day 21, day 30, day 60 (primary endpoint).

      During each visit, biological and clinical features including efficacy and tolerance will be
      assessed as well as presence of infection and hepatorenal syndrome (secondary endpoints).
    

Intervention name(s): Amoxicillin; Placebo; Prednisolone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Amoxicillin+clavulanic acid at a daily dose of 3 gram / 375 mg in three daily doses of 1g/125mg, during 30 days; Placebo in three daily doses during 30 days; Prednisolone at 40 mg/j in a single daily dose in the morning, during 30 days
Other intervention name(s): Amoxicillin + clavulanic acid; Placebo of amoxicillin; corticotherapy
Intervention MeSH terms: Amoxicillin; Clavulanic Acids; Clavulanic Acid; Amoxicillin-Potassium Clavulanate Combination; Prednisolone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcoholic hepatitis; corticotherapy; antibiotherapy; survival; infection; hepato renal syndrome