Corticosteroid plus pentoxifylline is not better than corticosteroid alone for improving survival in severe alcoholic hepatitis (COPE trial)

Dig Dis Sci. 2012 Jun;57(6):1664-71. doi: 10.1007/s10620-012-2097-4. Epub 2012 Mar 3.

Abstract

Background: Corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both drugs may lead to better survival, but has not yet been studied.

Aim: To compare the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids alone in improving survival of SAH patients.

Methods: Of the 111 patients screened, 70 patients with SAH (Maddrey discriminant function (MDF) ≥ 32) were enrolled. Patients with active infection, bleeding, renal failure, or pancreatitis were excluded. Treatment was given for four weeks to group A (n = 36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are expressed as median (range) or percentage.

Results: Baseline characteristics of the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6-140.2)). Four-week and six-month survival in groups A and B were not significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six-month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients in group A and 64.7% in group B had a Lille score <0.45 (p = 0.473). Six-month survival was significantly higher for patients with a Lille Score <0.45 than for those with a Lille score ≥0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs. 0%, p = 0.0304). Biological improvement at 28 days was significant for both groups; however, the difference between the groups was not significant.

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

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Aged
  • Analysis of Variance
  • Cause of Death*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Hepatitis, Alcoholic / diagnosis
  • Hepatitis, Alcoholic / drug therapy*
  • Hepatitis, Alcoholic / mortality*
  • Hospitalization / statistics & numerical data
  • Humans
  • India
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Pentoxifylline / administration & dosage*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Pentoxifylline