Corticosteroid Plus Pentoxifylline Is Not Better than Corticosteroid Alone for Improving Survival in Severe Alcoholic Hepatitis (COPE Trial)

Sidhu, Sandeep Singh; Singla, Puneet; Gupta, Dhiraj; Sood, Ajit; Chhina, Rajoo Singh; Soni, RK

doi:10.1007/s10620-012-2097-4

Cited by 70 publications

(45 citation statements)

References 32 publications

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“…As a result of the poor quality of most of the studies, the authors concluded that no conclusions could be drawn regarding whether pentoxifylline had a positive, negative, or neutral effect on participants with alcoholic hepatitis. Mathurin et al 6 found no evidence of an additive effect when pentoxifylline was added to prednisolone confirming the findings of the COPE trial 7 . Based on these published randomized controlled trials (RCT) and meta-analyses, prednisolone and pentoxifylline were incorporated in the past 5 years into guidelines of the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) 8,9 but these recommendations remained controversial due to the quality of the data upon which they were based.…”

Section: Discussionmentioning

confidence: 74%

Alcoholic hepatitis: Yes to prednisolone and no to pentoxifylline

Davies

Dezfulian

2016

F1000Res

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Section: Discussionmentioning

confidence: 74%

Alcoholic hepatitis: Yes to prednisolone and no to pentoxifylline

Davies

Dezfulian

2016

F1000Res

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“…In a study comparing pentoxifylline with corticosteroids, a benefi t in survival in the pentoxifylline group was observed, with 15 % 1-month mortality in pentoxifylline-treated patients vs. 35 % mortality in patients treated with corticosteroids [ 110 ]. In a second study, in which a combination of pentoxifylline and corticosteroids was compared with corticosteroids alone, no difference in survival was found; however, this study was not double-blind in design [ 111 ]. Experimental data have demonstrated the anti-infl ammatory and antitumor necrosis factor alpha effects of pentoxifylline [ 112 ], although its benefi t in severe alcoholic hepatitis seems to be related to the prevention of hepatorenal syndrome [ 103 , 109 ].…”

Section: Pentoxifyllinementioning

confidence: 92%

Treatment of Alcoholic Liver Disease Including Emerging Therapies, Novel Targets, and Liver Transplantation

Petrášek

Szabó

2016

Alcoholic and Non-Alcoholic Fatty Liver Disease

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“…23,24 Three small studies [25][26][27] have compared steroids directly with PTX but the results were inconsistent. One study 28 explored the use of PTX as a rescue therapy once steroids had failed to improve liver function tests (LFTs) but this strategy did not influence survival.…”

Section: Steroids And/or Pentoxifyllinementioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

Thursz

Forrest

Roderick

et al. 2015

Health Technol Assess

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BackgroundAlcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. 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.ObjectivesThe 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.DesignThe trial was a randomised, double-blind, 2 × 2 factorial, multicentre design.SettingSixty-five gastroenterology and hepatology inpatient units across the UK.ParticipantsPatients with a clinical diagnosis of AH who had a Maddrey’s discriminant function value of ≥ 32 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.InterventionsThose allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days.OutcomesThe 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.ResultsAt 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;p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01;p = 0.056). 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;p = 0.015). 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 (p = 0.002). 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.ConclusionsWe 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.Trial registrationThis trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; 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.

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Corticosteroid Plus Pentoxifylline Is Not Better than Corticosteroid Alone for Improving Survival in Severe Alcoholic Hepatitis (COPE Trial)

Abstract: For patients with severe alcoholic hepatitis, a combination of corticosteroids and pentoxifylline has no additional survival advantage compared with corticosteroids alone.

Cited by 70 publications

References 32 publications

Alcoholic hepatitis: Yes to prednisolone and no to pentoxifylline

Alcoholic hepatitis: Yes to prednisolone and no to pentoxifylline

Treatment of Alcoholic Liver Disease Including Emerging Therapies, Novel Targets, and Liver Transplantation

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

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