Corticosteroids in Alcoholic Hepatitis

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ClinicalTrials.gov Identifier: NCT03160651

Recruitment Status : Recruiting

First Posted : May 19, 2017

Last Update Posted : February 26, 2021

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Erasme University Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alcoholic Hepatitis	Drug: Methylprednisolone or placebo	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	140 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Masking Description:	double-blind randomized trial Investigator, patients, and care providers will be masking Only statisticians and pharmacist will not be masking
Primary Purpose:	Treatment
Official Title:	Corticosteroids in Severe Alcoholic Hepatitis Patients With Early Spontaneous Improvement
Actual Study Start Date :	February 9, 2018
Estimated Primary Completion Date :	June 2022
Estimated Study Completion Date :	December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis Hepatitis A Steroids

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: methylprednisolone Patients will receive 28 days of methylprednisolone 32 mg/day	Drug: Methylprednisolone or placebo Patients will receive 28 days of methylprednisolone 32 mg/day
Placebo Comparator: placebo Patients will receive 28 days of matching placebo	Drug: Methylprednisolone or placebo Patients will receive 28 days of methylprednisolone 32 mg/day

Outcome Measures

Primary Outcome Measures :

Mortality at 90 days [ Time Frame: 90 days ]
To determine whether Methylprednisolone compared to placebo improve the 90 day mortality from patients with severe AH and spontaneous improvement of liver function

Secondary Outcome Measures :

Mortality at 28 days [ Time Frame: 28 days ]
To determine the 28 day mortality from patients with severe AH and spontaneous liver function improvement treated with Methylprednisolone or placebo
Incidence of infections during the study period (90 days) [ Time Frame: 90 days ]
To determine the incidence of infections during the 90 day study period in corticosteroid-treated compared to placebo-treated patients

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)
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.
Spontaneous liver function improvement, defined by a decrease in serum bilirubin level > 10% between admission and day 5-10 after admission
less than 2 weeks since admission to hospital
Maddrey discriminant function* greater than or equal to 32
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.
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:

Other causes of liver disease including viral hepatitis (positive HBs antigen, HCV RNA positive), auto-immune hepatitis, biliary obstruction
Other disease compromising 90-day survival
Positive HIV serology
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.
Uncontrolled gastrointestinal bleeding Bleeding must be judged as controlled for at least 5 days
Patient with serum creatinine > 2.5 mg/dL, under renal replacement therapy or under terlipressine (or other vasoactive drugs)
Pentoxyphilline therapy
Pregnant or lactating women

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03160651

Contacts

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Contact: Christophe Moreno, MD, PhD	+32 2 5553714	christophe.moreno@erasme.ulb.ac.be
Contact: Françoise Smits, Nurse	+32 2 5554478	francoise.smits@erasme.ulb.ac.be

Locations

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Belgium
CUB Hôpital Erasme	Recruiting
Brussels, Belgium, 1070
Contact: Christophe Moreno, MD christophe.moreno@erasme.ulb.ac.be

Sponsors and Collaborators

Erasme University Hospital

Investigators

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Principal Investigator:	Christophe Moreno, MD, PhD	Erasme University Hospital

More Information

Publications:

Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009 Jun 25;360(26):2758-69. doi: 10.1056/NEJMra0805786. Review.

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.

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.

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.

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.

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. Review.

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.

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.

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Responsible Party:	Erasme University Hospital
ClinicalTrials.gov Identifier:	NCT03160651
Other Study ID Numbers:	CORTISAVE study
First Posted:	May 19, 2017 Key Record Dates
Last Update Posted:	February 26, 2021
Last Verified:	February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by Erasme University Hospital:


alcoholic hepatitis spontaneous improvement corticosteroids

Additional relevant MeSH terms:

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Hepatitis A Hepatitis Hepatitis, Alcoholic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Liver Diseases, Alcoholic Alcohol-Induced Disorders Alcohol-Related Disorders Substance-Related Disorders Chemically-Induced Disorders	Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Prednisolone hemisuccinate Prednisolone phosphate Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones

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