STOPAH: Steroids or pentoxifyline for alcoholic hepatitis
| ISRCTN | ISRCTN88782125 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN88782125 |
| Secondary identifying numbers | HTA 08/14/44 |
- Submission date
- 23/06/2009
- Registration date
- 26/06/2009
- Last edited
- 17/12/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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
Contact information
Scientific
Department of Hepatology
Imperial College London
Faculty of Medicine
St Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom
Study information
| Study design | Multicentre randomised double-blind factorial (2 x 2) design trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | STOPAH: STeroids Or Pentoxifyline for Alcoholic Hepatitis |
| Study 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(s) | Not provided at time of registration |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Pentoxifyline, prednisolone |
| Primary outcome measure | 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 study start date | 01/12/2009 |
| Overall study end date | 30/11/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1200 |
| Total final enrolment | 1068 |
| 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 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
- England
- United Kingdom
Study participating centre
W2 1PG
United Kingdom
Sponsor information
Hospital/treatment centre
Joint R&D Office, Mail Point 138
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
England
United Kingdom
| Website | http://www.suht.nhs.uk/home.aspx |
|---|---|
"ROR" |
https://ror.org/0485axj58 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 19/08/2013 | Yes | No | |
| Results article | results | 23/04/2015 | Yes | No | |
| Results article | results | 01/12/2015 | Yes | No | |
| Results article | results | 01/02/2021 | 17/12/2020 | Yes | No |
Editorial Notes
17/12/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
21/04/2016: Plain English summary added.
23/12/2015: Publication reference added.
