Assessment of the effect of a corticosteroids treatment in severe alcoholic hepatitis patients with early spontaneous improvement

Phase 1

• Conditions: severe alcoholic hepatitis; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2016-005136-16-BE
• Lead Sponsor: CUB Erasme Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-04-21
• Last Update Posted: 18 September 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1.Male or female, 18 years of age or older at time of screening
2.Clinical syndrome of alcoholic hepatitis: recent jaudice or in recent aggravation (< 3 months) serum bilirubin > 5 mg/dL history of excess alcohol abuse (> 40g/day)
3. Alcoholic hepatitis proven by a liver biopsy (histological criteria of alcoholic hepatitis defined according to EASL clinical practice guidelines : steatosis, hepatocyte ballooning, and an inflammatory infiltrate with PMNs). The results are not mandatory for inclusion. However, the biopsy must be planned at the latest on Day 1. When the results become available and don’t confirm the alcoholic hepatitis, the patient must discontinue the study.
4. Spontaneous liver function improvement, defined by a decrease in serum bilirubin level > 10% between admission and day 5-10 after admission
5. less than 2 weeks since admission to hospital
6. Maddrey discriminant function* greater than or equal to 32
7. Subjects must voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures.
8. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements.
Patients with significant hepatic encephalopathy are not excluded from participation to the trial. In this case, the patient should be accompanied by a legal representative that will decide participation in the clinical study and sign ICF.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

1. Other causes of liver disease including viral hepatitis (positive HBs antigen, HCV RNA positive), auto-immune hepatitis, biliary obstruction
2. Other disease compromising 90-day survival
3. Positive HIV serology
4. Uncontrolled infection
All patients will be screened for infection. This will involve chest radiography, urinalysis, PMNs count in ascites (if ascites present). All other sign or clinical suspicion of infection with or without antibiotherapy will be recorded as an infection.
Positive culture and initiation of antibiotics with clinical or radiological signs of infection, as well as clinical suspicion, will be recorded as infection.
Patients with evidence of sepsis will be treated for a minimum of 2 days with appropriate antibiotics. Once the local principal investigator considers that the sepsis is under control, the patient may be rescreened and randomised.
5. Uncontrolled gastrointestinal bleeding
Bleeding must be judged as controlled for at least 5 days
6. Patient with serum creatinine > 2.5 mg/dL, under renal replacement therapy or under terlipressine (or other vasoactive drugs)
7. Pentoxyphilline therapy
8. Pregnant or lactating women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the impact of methylprednisolone on the reduction of mortality at 90 days in patients with severe alcoholic hepatitis and who have demonstrated an early spontaneous improvement;Secondary Objective: To evaluate the mortality rate at 28 days <br>To estimate the number of infection (including bacterial, viral and fungal infections) at 90 days<br>;Primary end point(s): Mortality at 90 days;Timepoint(s) of evaluation of this end point: At 90 days

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Mortality at 28 days<br>- Incidence of infections during the study period (90 days) <br>- Incidence of Hepatorenal syndrome during the study period (90 days)<br>- Assessment and comparison of biochemical response to therapy at Day 7 between both groups (fall in total bilirubin and Lille score). <br>;Timepoint(s) of evaluation of this end point: At 7 days: Assessment and comparison of biochemical response <br>At 28 days: Mortality<br>At 90 days : Incidence of infections and Hepatorenal syndrome