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Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objectives<\/jats:title><jats:p>The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>The trial was a randomised, double-blind, 2\u2009\u00d7\u20092 factorial, multicentre design.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>Sixty-five gastroenterology and hepatology inpatient units across the UK.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Patients with a clinical diagnosis of AH who had a Maddrey\u2019s discriminant function value of \u2265\u200932 were randomised into four arms: A, placebo\/placebo; B, placebo\/prednisolone; C, PTX\/placebo; and D, PTX\/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Those allocated to prednisolone were given 40\u2009mg daily for 28 days and those allocated to PTX were given 400\u2009mg three times per day for 28 days.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Outcomes<\/jats:title><jats:p>The primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>At 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40;<jats:italic>p<\/jats:italic>\u2009=\u20090.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01;<jats:italic>p<\/jats:italic>\u2009=\u20090.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91;<jats:italic>p<\/jats:italic>\u2009=\u20090.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Conclusions<\/jats:title><jats:p>We conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Trial registration<\/jats:title><jats:p>This trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 19, No. 102. See the NIHR Journals Library website for further project information. The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta191020","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T13:40:00Z","timestamp":1450791600000},"page":"1-104","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2\u2009\u00d7\u20092 factorial randomised controlled trial"],"prefix":"10.3310","volume":"19","author":[{"given":"Mark","family":"Thursz","sequence":"first","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewan","family":"Forrest","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Glasgow 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