Open Access Study protocol

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

Ewan Forrest1, Jane Mellor2, Louise Stanton2, Megan Bowers2, Priscilla Ryder14, Andrew Austin3, Christopher Day4, Dermot Gleeson5, John O’Grady6, Steven Masson7, Anne McCune8, David Patch9, Paul Richardson10, Paul Roderick11, Stephen Ryder12, Mark Wright13 and Mark Thursz14*

Author Affiliations

1 Department of Gastroenterology, Glasgow Royal Infirmary, Castle Street, Glasgow G4 0SF, UK

2 University of Southampton Clinical Trials Unit, MP 131, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

3 Royal Derby Hospital, Faculty of Medical Sciences, Uttoxeter Road, Derby DE22 3NE, UK

4 Newcastle University Medical School Framlington Place, Newcastle upon Tyne NE2 4HH, UK

5 Liver Unit, Royal Hallamshire Hospital, Sheffield, UK

6 Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK

7 Liver Unit, Freeman Hospital, Freeman Road High Heaton, Newcastle upon Tyne NE7 7DN, UK

8 Department of Hepatology, Level 2, Old Building, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK

9 The Royal Free, Sheila Sherlock Liver Centre, The Royal Free Hospital, Pond Street, London NW3 2QG, UK

10 The Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK

11 Public Health Sciences and Medical Statistics, University of Southampton, C floor South Academic Block, Southampton General Hospital, Southampton SO16 6YD, UK

12 Department of Gastroenterology, Queen’s Medical Centre campus, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK

13 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

14 Hepatology Section, Imperial College, Norfolk Place, London, Paddington W2 1NY, UK

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Trials 2013, 14:262  doi:10.1186/1745-6215-14-262

Published: 19 August 2013

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 / placebo

2. Group B: placebo / prednisolone

3. Group C: pentoxifylline / placebo

4. Group D: pentoxifylline / prednisolone

The 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

Keywords:
Factorial design; Alcoholic hepatitis; Prednisolone; Pentoxifylline; Maddrey’s discriminant function (DF); Glasgow alcoholic hepatitis score (GAHS)