NCT01214226

Double-blind Randomized Controlled Trial in Severe Alcoholic Hepatitis

Evaluation of the Survival Benefit of the Adjunction of Pentoxifylline to Corticosteroids in Patients Suffering From Severe Alcoholic Hepatitis

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 278 (actual)
• Sponsor: University Hospital, Lille · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge for clinicians involved in the management of severe alcoholic liver disease. In patients with Maddrey function higher than 32, compelling evidence from data has shown that corticosteroids improve short-term survival. However, novel strategies or molecules are required in light of the fact that approximately 40 % of patients continue to die at 6 months. A double-blinded randomized controlled trial of 101 patients has showed that Pentoxifylline improves survival of patients with severe AH, as compared to placebo. In terms of mechanisms, the effect of pentoxifylline is related to prevention of hepatorenal function whereas corticosteroids induce an early improvement in liver function. When considering these differences of mechanisms, many clinicians suggest that the addition of pentoxyfilline to corticosteroids is an attractive option that needs to be tested in patients with severe AH.

Detailed description

The aim of the present study is to determine whether or not the adjunction of Pentoxifylline to corticosteroids would improve 6-month survival of patients with severe alcoholic hepatitis. This multicenter, randomized, double-blinded, controlled, phase 3 trial was conducted in 24 centers located in France and Belgium. Alcoholic hepatitis was biopsy-proven. All eligible patients were randomly assigned in a 1:1 ratio to receive corticosteroids + Pentoxifylline or corticosteroids + Placebo. The primary outcome of the study was 6-month survival. Assuming a two-sided type I error of 0.05, a randomization ratio of 1:1 between the 2 groups, 6-month survival of 64% in the Placebo and Corticosteroids group and of 78 % in the Pentoxifylline and Corticosteroids group, we estimated that with 268 randomized patients (134 in each group), the study would have a power of 80% to detect this increase in 6-month survival in the Pentoxifylline and Corticosteroid group.

Conditions

• Alcoholic Hepatitis
• Alcoholic Liver Disease

Interventions

Type	Name	Description
DRUG	Pentoxifylline	400 mg prolonged-released tablets 3 time per day for 1 month.
DRUG	placebo	prolonged-release tablets 3 time per day for 1 month

Timeline

• Start date: 2007-12-01
• Primary completion: 2010-12-01
• Completion: 2011-01-01
• First posted: 2010-10-04
• Last updated: 2011-06-01

Locations

28 sites across 2 countries: Belgium, France