COMPARATIVE STUDY
JOURNAL ARTICLE
MULTICENTER STUDY
RANDOMIZED CONTROLLED TRIAL

Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial

Philippe Mathurin, Alexandre Louvet, Alain Duhamel, Pierre Nahon, Nicolas Carbonell, Jérôme Boursier, Rodolphe Anty, Emmanuel Diaz, Dominique Thabut, Romain Moirand, Didier Lebrec, Christophe Moreno, Nathalie Talbodec, Thierry Paupard, Sylvie Naveau, Christine Silvain, Georges-Philippe Pageaux, Rodolphe Sobesky, Valérie Canva-Delcambre, Sébastien Dharancy, Julia Salleron, Thong Dao
JAMA: the Journal of the American Medical Association 2013 September 11, 310 (10): 1033-41
24026598

IMPORTANCE: Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown.

OBJECTIVE: To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome.

INTERVENTION: Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days.

MAIN OUTCOMES AND MEASURES: Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment.

RESULTS: In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07).

CONCLUSION AND RELEVANCE: In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01214226.

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