Efficacy of Antibiotic Therapy in Severe Alcoholic Hepatitis Treated With Prednisolone (AntibioCor)

December 15, 2025 updated by: University Hospital, Lille

Evaluation of the Efficacy of an Antibiotic Combined With Standard Treatment in Severe Alcoholic Hepatitis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

297

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France
        • CHU d'Amiens
      • Angers, France
        • CHU
      • Besançon, France
        • CHU de Besancon
      • Bondy, France, 93143
        • Hôpital Jean Verdier (AH-HP)
      • Caen, France
        • CHU de Caen
      • Clichy, France
        • Hôpital BEaujon (AP-HP)
      • Dunkirk, France
        • Centre Hospitalier
      • Grenoble, France
        • CHU Grenoble
      • Lille, France
        • Hôpital Claude Huriez, CHU
      • Montpellier, France
        • CHU Montpellier
      • Nantes, France
        • CHU Nantes
      • Nice, France
        • CHU Nice
      • Paris, France, 75012
        • Hôpital Saint Antoine (AP-HP)
      • Paris, France
        • Hôpital La Pitié (AP-HP)
      • Poitiers, France
        • CHU Poitiers
      • Rennes, France
        • Chu Pontchaillou
      • Rouen, France
        • CHU
      • Toulouse, France
        • CHU
      • Valenciennes, France, 59300
        • Centre Hospitalier
      • Villejuif, France, 94000
        • Hôpital Paul Brousse (AH-HP)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged 18-75
  • Recent onset of jaundice (<3 months)
  • Biopsy proven alcoholic hepatitis (transjugular liver biopsy)
  • Maddrey's discriminant function ≥ 32, defining severe alcoholic hepatitis
  • MELD score ≥21
  • Alcohol consumption ≥ 40g/day (women) and ≥ 50g/day (men)
  • Written informed consent

Exclusion Criteria:

  • Previous severe allergy or hypersensitivity to amoxicillin or clavulanic acid (anaphylactic shock, Quincke edema, severe urticaria)
  • Hypersensitivity to any component of the medication
  • History of liver injury to amoxicillin and/or clavulanic acid
  • Phenylketonuria, because of the presence of aspartame in the powder for the oral suspension
  • Type 1 hepatorenal syndrome before the initiation of treatment
  • Severe extrahepatic disease
  • Any malignant tumor < 2 years
  • Uncontrolled gastrointestinal bleeding
  • Ongoing viral or parasitic infection
  • Untreated bacterial infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: amoxicillin+ prednisolone
Oral antibiotherapy during 30 days using amoxicillin+clavulanic acid at a daily dose of 3 gram (amoxicillin) and 375 mg (clavulanic acid) in three daily doses of 1g/125mg. Oral corticotherapy during 30 days with prednisolone at 40 mg/j in a single daily dose in the morning.
Drug: Amoxicillin
Amoxicillin+clavulanic acid at a daily dose of 3 gram / 375 mg in three daily doses of 1g/125mg, during 30 days
Other Names:
  • Amoxicillin + clavulanic acid
Drug: Prednisolone
Prednisolone at 40 mg/j in a single daily dose in the morning, during 30 days
Other Names:
  • corticotherapy
Placebo Comparator: Placebo + prednisolone
Oral placebo of amoxicillin- clavulanic acid in three daily doses during 30 days Oral corticotherapy during 30 days with prednisolone at 40 mg/j in a single daily dose in the morning.
Drug: Prednisolone
Prednisolone at 40 mg/j in a single daily dose in the morning, during 30 days
Other Names:
  • corticotherapy
Drug: Placebo
Placebo in three daily doses during 30 days
Other Names:
  • Placebo of amoxicillin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient alive
Time Frame: at day 60
The percentage of patients alive at 2 months in the experimental arm compared to the percentage of patients alive in the control arm
at day 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infection
Time Frame: at day 7, day14, day 21, day 30, day 60; at 3 months, at 6 months
incidence of infection over the 2-month period in the antibiotic+corticosteroid arm as compared to the control arm
at day 7, day14, day 21, day 30, day 60; at 3 months, at 6 months
Hepatorenal syndrome
Time Frame: at day 7, day14, day 21, day 30,at 3 months, at 6 months
incidence of hepatorenal syndrome over the 2-month period in the antibiotic+corticosteroid arm as compared to the control arm
at day 7, day14, day 21, day 30,at 3 months, at 6 months
MELD score <17
Time Frame: at day 7, day14, day 21, day 30,
percentage of patients with a low risk of mortality during the first two months (assessed by a MELD score <17) in the two arms of treatment. The MELD score will be calculated using the following formula:(9.57 × log creatinine in milligrams per deciliter) + (3.78 × log bilirubin in milligrams per deciliter) + (11.20 × log international normalized ratio) + 6.43.
at day 7, day14, day 21, day 30,
Lille Model
Time Frame: at day 7, after the first administration of treatment
percentage of patients disclosing a response to treatment assessed by the Lille model (<0.45) in the two arms of treatment.
at day 7, after the first administration of treatment
Patient alive
Time Frame: at 3 months, at 6 months
The percentage of patients alive at 2 months in the experimental arm compared to the percentage of patients alive in the control arm
at 3 months, at 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

Ministry of Health, France

Investigators

  • Study Chair: Mathurin Philippe, MD,PhD, University Hospital, Lille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2015

Primary Completion (Actual)

November 19, 2019

Study Completion (Actual)

November 19, 2019

Study Registration Dates

First Submitted

October 28, 2014

First Submitted That Met QC Criteria

October 30, 2014

First Posted (Estimated)

November 4, 2014

Study Record Updates

Last Update Posted (Estimated)

December 22, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014_05
  • 2014-002536-13 (EudraCT Number)
  • PHRC-2013-0552 (Other Identifier: Minister of Health, France)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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