Corticosteroids in Alcoholic Hepatitis

NCT03160651 | Unknown DMC

• 1 other identifier: CORTISAVE study
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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

Conditions

Alcoholic Hepatitis

Keywords

alcoholic hepatitis; spontaneous improvement; corticosteroids

Outcome Measures

Primary Outcomes (1)

• Mortality at 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

  90 days

Secondary Outcomes (2)

• Mortality at 28 days

  28 days

• Incidence of infections during the study period (90 days)

  90 days

Study Arms (2)

methylprednisolone

ACTIVE COMPARATOR

Patients will receive 28 days of methylprednisolone 32 mg/day

Drug: Methylprednisolone or placebo

placebo

PLACEBO COMPARATOR

Patients will receive 28 days of matching placebo

Drug: Methylprednisolone or placebo

Interventions

Methylprednisolone or placebo DRUG

Patients will receive 28 days of methylprednisolone 32 mg/day

methylprednisolone; placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasme University Hospital: lead

Study Sites (1)

CUB Hôpital Erasme

Brussels, 1070, Belgium

RECRUITING

Related Publications (8)

• 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.

  PMID: 19553649 BACKGROUND

• 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.

  PMID: 352788 BACKGROUND

• 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.

  PMID: 11943418 BACKGROUND

• 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.

  PMID: 2648927 BACKGROUND

• 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.

  PMID: 22633836 BACKGROUND

• 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.

  PMID: 20034030 BACKGROUND

• 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.

  PMID: 20940288 BACKGROUND

• 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.

  PMID: 25901427 BACKGROUND

MeSH Terms

Conditions

Hepatitis, Alcoholic

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christophe Moreno, MD, PhD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christophe Moreno, MD, PhD

CONTACT

+32 2 5553714; christophe.moreno@erasme.ulb.ac.be

Françoise Smits, Nurse

CONTACT

+32 2 5554478; francoise.smits@erasme.ulb.ac.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind randomized trial Investigator, patients, and care providers will be masking Only statisticians and pharmacist will not be masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: May 19, 2017
• Study Start: February 9, 2018
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 26, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)