Condition category
Digestive System
Date applied
23/06/2009
Date assigned
26/06/2009
Last edited
21/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
In the UK the number of deaths caused by liver disease is increasing dramatically, and the leading cause of liver disease is excess alcohol consumption. Alcohol misuse over a long period leads to alcoholic hepatitis, where there is marked inflammation in the liver. The death rate amongst patients with severe alcoholic hepatitis is over 30% within the first month after admission to hospital. Several studies have shown an improvement in survival rates with the use of prednisolone, a corticosteroid drug which suppresses inflammation. However, other studies, many of which have been criticised for their small size or poor quality, found no benefit to steroid use. In many units around the UK prednisolone is now accepted as standard treatment for severe alcoholic hepatitis but this practice is not consistent and a definitive study is therefore required to determine the best treatment option. A second drug, pentoxifylline, has been shown to be effective in patients with severe alcoholic hepatitis. Pentoxifylline has also been shown to reduce resistance to corticosteroids and might therefore act together with prednisolone to reduce death rates in patients with severe alcoholic hepatitis. Unfortunately only one study of pentoxifylline alone and one study of pentoxifylline in combination with prednisolone have been reported and conclusions about the effectiveness of the drug are therefore hard to draw. The aim of this study is to evaluate the effectiveness of prednisolone and pentoxifylline in patients with severe alcoholic hepatitis.

Who can participate?
Patients aged 18 or over with alcoholic hepatitis

What does the study involve?
Participants are randomly allocated into four groups: a group treated with a placebo (dummy drug), a group treated with prednisolone alone, a group on pentoxifylline alone, and a group on both prednisolone and pentoxifylline. We then measure patient survival after 28 days, 3 months and 12 months, and the development of any disease/treatment complications.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
December 2009 to November 2013

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Prof Mark Thursz

Trial website

Contact information

Type

Scientific

Primary contact

Prof Mark Thursz

ORCID ID

Contact details

Department of Hepatology
Imperial College London
Faculty of Medicine
St Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 08/14/44

Study information

Scientific title

STOPAH: STeroids Or Pentoxifyline for Alcoholic Hepatitis

Acronym

STOPAH

Study hypothesis

The primary objective of this study is to determine whether pentoxifylline (PTX) or corticosteroids reduce the mortality associated with severe alcoholic hepatitis.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/081444
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0004/81373/PRO-08-14-44.pdf

Ethics approval

Not provided at time of registration

Study design

Multicentre randomised double-blind factorial (2 x 2) design trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Alcoholic hepatitis

Intervention

The planned interventions will be prednisolone (40 mg for 4 weeks) or pentoxifylline (400 mg 3 times a day for 4 weeks):
1. Group A: placebo/placebo
2. Group B: placebo/prednisolone
3. Group C: pentoxifylline/placebo
4. Group D: pentoxifylline/prednisolone

Intervention type

Drug

Phase

Phase III

Drug names

Pentoxifyline, prednisolone

Primary outcome measures

Mortality at 28 days

Secondary outcome measures

1. Mortality at 3 and 12 months
2. Outcome relative to Glasgow Alcoholic Hepatitis Score
3. Assessment of biochemical response to treatment
4. Duration of hospitalisation
5. The development of new or recurrent renal failure
6. Development of gastro-intestinal haemorrhage and sepsis
7. Incremental NHS costs and quality of life at 3 and 12 months

Overall trial start date

01/12/2009

Overall trial end date

30/11/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Clinical alcoholic hepatitis:
1.1. Serum bilirubin greater than 80 µmol/L
1.2. History of excess alcohol (greater than 80 g/day male, greater than 60 g/day female)
2. Less than 4 weeks from admission to hospital
3. Discriminant Function (DF) greater than or equal to 32
4. Informed consent
5. Minimum 18 years old, no upper limit, either sex

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1200

Participant exclusion criteria

1. Abstinence of more than 6 weeks prior to randomisation
2. Duration of jaundice greater than 3 months
3. Other causes of liver disease
4. Evidence of current malignancy (except non-melanotic skin cancer)
5. Previous entry into the study, or use of either prednisolone or PTX within 6 months
6. Aspartate aminotransferase (AST) greater than 500 or alanine aminotransferase (ALT) greater than 300
7. Patients with a serum creatinine greater than 500 µmol/L or requiring renal support
8. Patients dependent upon inotropic support
9. Active gastro-intestinal haemorrhage and untreated sepsis

Recruitment start date

01/12/2009

Recruitment end date

30/11/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College London
London
W2 1PG
United Kingdom

Sponsor information

Organisation

Southampton University Hospitals NHS Trust (UK)

Sponsor details

Joint R&D Office
Mail Point 138
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor type

Government

Website

http://www.suht.nhs.uk/home.aspx

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23958271
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/25901427
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26691209

Publication citations

  1. Protocol

    Forrest E, Mellor J, Stanton L, Bowers M, Ryder P, Austin A, Day C, Gleeson D, O'Grady J, Masson S, McCune A, Patch D, Richardson P, Roderick P, Ryder S, Wright M, Thursz M, Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial., Trials, 2013, 14, 262, doi: 10.1186/1745-6215-14-262.

  2. Results

    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, 372, 17, 1619-1628, doi: 10.1056/NEJMoa1412278.

Additional files

Editorial Notes

21/04/2016: Plain English summary added. 23/12/2015: Publication reference added.