Case study: STOPAH
In the UK, the mortality rate from alcoholic liver disease is rising rapidly, and so STOPAH is considered as a vitally important study, being more than ten times larger than any previous study in this patient population. 61 UK hospitals recruited for the study which achieved more than 1100 participants and it will provide key answers to vital therapeutic questions and alter clinical practice when analysis is complete.Find out more
STOPAH - STeroids Or Pentoxifylline for Alcoholic Hepatitis
• The study ran from 2011 - 2014
• 1103 patients with alcoholic hepatitis were recruited to the study by the NIHR
• The study was delivered from 65 NIHR funded sites
• Funded by NIHR Health Technology Assessment (HTA) Programme
• Chief Investigator: Professor Mark Thursz at Imperial College and Consultant in hepatology at St Mary’s Hospital, London
• STOPAH has stimulated investment in research into the mechanisms of liver disease, identifying targets for new treatments, and developing better strategies to stop people drinking.
In the UK the number of deaths caused by liver disease is increasing, and the leading cause of liver disease is excess alcohol consumption. Alcohol misuse over a long period leads to alcoholic hepatitis, this is where there is marked inflammation in the liver. The death rate amongst patients with severe alcoholic hepatitis is over 30 per cent within the first month after admission to hospital.
Prednisolone (steroid treatment) and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis and are widely used, but uncertainty remained about their benefits. STOPAH was a randomised double blind trial designed to evaluate the effect of treatment with prednisolone or pentoxifylline in patients with alcoholic hepatitis. This study was four times larger than any previous study into this condition to provide stronger data about effective use of the drugs. The NIHR supported the study and recruited 1103 patients with alcoholic hepatitis who were randomly assigned to one of the four treatment groups. As the condition significantly shortens life, the primary outcome measure was mortality at 28 days.
Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. The study also looked at if patients started to drink excess levels of alcohol again or entered into rehabilitation programmes.
Outcomes and findings
The study found that neither treatment had a significant effect on survival after the first 28 days. Of the four controlled arms of the trial, the group which received the prednisolone alone reduced the risk of death at 28 days the most. However the effect was relatively weak and did not continue. The group which took the pentoxifylline alone had the highest mortality rate at 28 days. At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups.
After 1 year, half the patients had died or had a liver transplant. 37% had stopped drinking alcohol and 20% attended an alcohol rehabilitation programme. In the longer term, more effort needs to be made to get patients into rehabilitation programmes. New treatments are required to suppress the inflammation in the liver without increasing the risk of infection.
“We were surprised to find that neither treatment had a significant effect on survival after the first month, and the mortality rate after one year is alarmingly high. The STOPAH trial has stimulated the investment in research into the mechanisms of liver disease, identify targets for new treatments, and developing better strategies to stop people drinking.”
Professor Mark Thursz at Imperial College, Consultant in hepatology at St Mary’s Hospital, London and Chief Investigator on the STOPAH.
Value to the NHS
There is a lot of value in questioning and investigating practices that seem to make sense but may be costly and dangerous. The STOPAH trial illustrated that neither of these medical treatments help in the medium to long term and that treatment with steroids increases the risk of serious infections.
This trial has enabled us to stop doing things that don’t work and increased our focus on finding new things that might help. The results of this study has opened up more research into this area and the recommended use of pentoxifylline for the treatment of alcoholic hepatitis has been removed from the NICE guidelines.
• M.R. Thursz et al. ‘Prednisolone or Pentoxifylline for Alcoholic Hepatitis.’ N Engl J Med 2015;372:1619-28. DOI: 10.1056/NEJMoa1412278
• The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2×2 factorial randomised controlled trial. https://www.ncbi.nlm.nih.gov/pubmed/26691209