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Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial

Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial
Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial

Background: alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey's discriminant function (DF) ≥32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published.

Methods/design: STOPAH is a multicentre, double-blind, factorial (2 × 2) trial in which patients are randomised to one of four groups:1. Group A: placebo / placebo2. Group B: placebo / prednisolone3. Group C: pentoxifylline / placebo4. Group D: pentoxifylline / prednisoloneThe trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary endpoints being mortality at 90 days and 1 year.

Discussion: STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power.

Trial registration: EudraCT reference number: 2009-013897-42 ISRCTN reference number: ISRCTN88782125.

Clinical Protocols, Double-Blind Method, Fatty Liver, Alcoholic/diagnosis, Glucocorticoids/therapeutic use, Humans, Kaplan-Meier Estimate, Pentoxifylline/therapeutic use, Prednisolone/therapeutic use, Research Design, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, United Kingdom
1745-6215
Forrest, Ewan
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Mellor, Jane
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Stanton, Louise
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Bowers, Megan
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Ryder, Priscilla
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Austin, Andrew
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Day, Christopher
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Gleeson, Dermot
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O'Grady, John
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Masson, Steven
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McCune, Anne
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Patch, David
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Richardson, Paul
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Roderick, Paul
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Ryder, Stephen
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Wright, Mark
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Thursz, Mark
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Forrest, Ewan
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Mellor, Jane
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Stanton, Louise
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Bowers, Megan
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Ryder, Priscilla
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Austin, Andrew
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Day, Christopher
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Gleeson, Dermot
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O'Grady, John
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Masson, Steven
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McCune, Anne
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Patch, David
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Richardson, Paul
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Roderick, Paul
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Ryder, Stephen
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Wright, Mark
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Thursz, Mark
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Forrest, Ewan, Mellor, Jane, Stanton, Louise, Bowers, Megan, Ryder, Priscilla, Austin, Andrew, Day, Christopher, Gleeson, Dermot, O'Grady, John, Masson, Steven, McCune, Anne, Patch, David, Richardson, Paul, Roderick, Paul, Ryder, Stephen, Wright, Mark and Thursz, Mark (2013) Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial. Trials, 14, [262]. (doi:10.1186/1745-6215-14-262).

Record type: Article

Abstract

Background: alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey's discriminant function (DF) ≥32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published.

Methods/design: STOPAH is a multicentre, double-blind, factorial (2 × 2) trial in which patients are randomised to one of four groups:1. Group A: placebo / placebo2. Group B: placebo / prednisolone3. Group C: pentoxifylline / placebo4. Group D: pentoxifylline / prednisoloneThe trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary endpoints being mortality at 90 days and 1 year.

Discussion: STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power.

Trial registration: EudraCT reference number: 2009-013897-42 ISRCTN reference number: ISRCTN88782125.

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1745-6215-14-262 - Version of Record
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Accepted/In Press date: 30 July 2013
Published date: 19 August 2013
Keywords: Clinical Protocols, Double-Blind Method, Fatty Liver, Alcoholic/diagnosis, Glucocorticoids/therapeutic use, Humans, Kaplan-Meier Estimate, Pentoxifylline/therapeutic use, Prednisolone/therapeutic use, Research Design, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, United Kingdom
Organisations: Primary Care & Population Sciences, Clinical Trials Unit

Identifiers

Local EPrints ID: 366067
URI: http://eprints.soton.ac.uk/id/eprint/366067
ISSN: 1745-6215
PURE UUID: 2faba3a0-31fc-4138-a465-c3d537327a17
ORCID for Louise Stanton: ORCID iD orcid.org/0000-0001-8181-840X
ORCID for Paul Roderick: ORCID iD orcid.org/0000-0001-9475-6850

Catalogue record

Date deposited: 20 Jun 2014 10:53
Last modified: 15 Mar 2024 03:28

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Contributors

Author: Ewan Forrest
Author: Jane Mellor
Author: Louise Stanton ORCID iD
Author: Megan Bowers
Author: Priscilla Ryder
Author: Andrew Austin
Author: Christopher Day
Author: Dermot Gleeson
Author: John O'Grady
Author: Steven Masson
Author: Anne McCune
Author: David Patch
Author: Paul Richardson
Author: Paul Roderick ORCID iD
Author: Stephen Ryder
Author: Mark Wright
Author: Mark Thursz

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