Corticosteroids in Alcoholic Hepatitis

NCT ID: NCT03160651

Last Updated: 2021-02-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-09

Study Completion Date

2022-12-31

Brief Summary

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Approximately 50% of patients admitted for severe AH will have spontaneous improvement of liver function before initiation of therapy (ie decrease in mDF between hospital admission and initiation of steroids). These patients have a better prognosis than patients without spontaneous improvement of liver function. It has never been demonstrated that corticosteroids improve survival in severe AH patients with spontaneous improvement of liver function. Our hypothesis is that severe AH patients with spontaneous improvement of liver function represent a group who could most benefit from steroids

Detailed Description

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Conditions

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Alcoholic Hepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
double-blind randomized trial Investigator, patients, and care providers will be masking Only statisticians and pharmacist will not be masking

Study Groups

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methylprednisolone

Patients will receive 28 days of methylprednisolone 32 mg/day

Group Type ACTIVE_COMPARATOR

Methylprednisolone or placebo

Intervention Type DRUG

Patients will receive 28 days of methylprednisolone 32 mg/day

placebo

Patients will receive 28 days of matching placebo

Group Type PLACEBO_COMPARATOR

Methylprednisolone or placebo

Intervention Type DRUG

Patients will receive 28 days of methylprednisolone 32 mg/day

Interventions

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Methylprednisolone or placebo

Patients will receive 28 days of methylprednisolone 32 mg/day

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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)
2. 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 of the liver biopsy are not mandatory for inclusion. However, the biopsy must be planned at the latest on day 1. When the results become available and do not confirm alcoholic hepatitis, the patient must discontinue the study.
3. Spontaneous liver function improvement, defined by a decrease in serum bilirubin level \> 10% between admission and day 5-10 after admission
4. less than 2 weeks since admission to hospital
5. Maddrey discriminant function\* greater than or equal to 32
6. 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.
7. 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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erasme University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christophe Moreno, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasme University Hospital

Locations

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CUB Hôpital Erasme

Brussels, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Christophe Moreno, MD, PhD

Role: CONTACT

+32 2 5553714

Françoise Smits, Nurse

Role: CONTACT

+32 2 5554478

Facility Contacts

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Christophe Moreno, MD

Role: primary

References

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Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009 Jun 25;360(26):2758-69. doi: 10.1056/NEJMra0805786. No abstract available.

Reference Type BACKGROUND
PMID: 19553649 (View on PubMed)

Maddrey WC, Boitnott JK, Bedine MS, Weber FL Jr, Mezey E, White RI Jr. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978 Aug;75(2):193-9.

Reference Type BACKGROUND
PMID: 352788 (View on PubMed)

Mathurin P, Mendenhall CL, Carithers RL Jr, Ramond MJ, Maddrey WC, Garstide P, Rueff B, Naveau S, Chaput JC, Poynard T. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002 Apr;36(4):480-7. doi: 10.1016/s0168-8278(01)00289-6.

Reference Type BACKGROUND
PMID: 11943418 (View on PubMed)

Carithers RL Jr, Herlong HF, Diehl AM, Shaw EW, Combes B, Fallon HJ, Maddrey WC. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med. 1989 May 1;110(9):685-90. doi: 10.7326/0003-4819-110-9-685.

Reference Type BACKGROUND
PMID: 2648927 (View on PubMed)

European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol. 2012 Aug;57(2):399-420. doi: 10.1016/j.jhep.2012.04.004. Epub 2012 May 26. No abstract available.

Reference Type BACKGROUND
PMID: 22633836 (View on PubMed)

O'Shea RS, Dasarathy S, McCullough AJ; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010 Jan;51(1):307-28. doi: 10.1002/hep.23258. No abstract available.

Reference Type BACKGROUND
PMID: 20034030 (View on PubMed)

Mathurin P, O'Grady J, Carithers RL, Phillips M, Louvet A, Mendenhall CL, Ramond MJ, Naveau S, Maddrey WC, Morgan TR. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011 Feb;60(2):255-60. doi: 10.1136/gut.2010.224097. Epub 2010 Oct 12.

Reference Type BACKGROUND
PMID: 20940288 (View on PubMed)

Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, Downs N, Gleeson D, MacGilchrist A, Grant A, Hood S, Masson S, McCune A, Mellor J, O'Grady J, Patch D, Ratcliffe I, Roderick P, Stanton L, Vergis N, Wright M, Ryder S, Forrest EH; STOPAH Trial. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015 Apr 23;372(17):1619-28. doi: 10.1056/NEJMoa1412278.

Reference Type BACKGROUND
PMID: 25901427 (View on PubMed)

Other Identifiers

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CORTISAVE study

Identifier Type: -

Identifier Source: org_study_id

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