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CorpentoxHAA: Double-blind Randomized Controlled Trial in Severe Alcoholic Hepatitis

Sponsor
University Hospital, Lille (Other)
Overall Status
Completed
CT.gov ID
NCT01214226
Collaborator
Ministry of Health, France (Other)
278
Enrollment
28
Locations
2
Arms
37
Duration (Months)
9.9
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
278 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Evaluation of the Survival Benefit of the Adjunction of Pentoxifylline to Corticosteroids in Patients Suffering From Severe Alcoholic Hepatitis
Study Start Date :
Dec 1, 2007
Actual Primary Completion Date :
Dec 1, 2010
Actual Study Completion Date :
Jan 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Pentoxifylline + Prednisolone

Pentoxifylline 400 mg prolonged-released tablets 3 time a day [1200 mg/day] + Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]

Drug: placebo
prolonged-release tablets 3 time per day for 1 month
Placebo Comparator: Placebo + Prednisolone

Placebo prolonged-release tabled 3 time a day + Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]

Drug: Pentoxifylline
400 mg prolonged-released tablets 3 time per day for 1 month.
Other Names:
  • TORENTAL 400MG

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [6 months]

    Secondary Outcome Measures

    1. Hepatorenal syndrome [6 months]

    2. Score of Lille model [Seven days]

    3. Percentage of Meld score (Model for End-stage Liver Disease) higher than 17 [6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Alcohol consumption more than 40 gram/day for women and 50 gram/day for men

    • Maddrey discriminant function higher than 32

    • Onset of jaundice within the 3 previous months

    • Biopsy-proven alcoholic hepatitis

    Exclusion Criteria:

    • Hypersensitivity to pentoxifylline

    • Any severe disease that may potential affect survival such as cardiac failure, ischemic cardiopathy, respiratory failure

    • Any neoplasm that occurred within the 2 previous years

    • Hepatocellular carcinoma or any previous diagnosis of hepatocellular carcinoma

    • Portal thrombosis

    • Severe gastrointestinal bleeding

    • Uncontrolled sepsis within the 7 previous days

    • Hepatorenal syndrome type I

    • Viral and fungal infection

    • Acute pancreatitis

    • Any tuberculosis that occurred within the 5 previous years

    • Psychiatric disorders that contraindicate the use of corticosteroids

    • Infection related to virus of the hepatites B or C

    • HIV infection (Human immunodeficiency virus)

    • Any treatment with corticosteroids, immunosuppressive agents, budesonide, thalidomide or pentoxifylline that was given within the previous year

    • Pregnancy or breast feeding

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University hospital Brussel Belgium 1070
    2 University hospital Angers France 49933
    3 Hôpital Jean Verdier (AH-HP) Bondy France 93143
    4 University hospital Bordeaux France 33000
    5 Centre hospitalier Béthune France 62408
    6 University hospital Caen France 14000
    7 Hospital Antoine Béclère (Assistance Publique des Hôpiaux de Paris) Clamart France 92141
    8 Hôpital Beaujon (AH-HP) Clichy France 92118
    9 Centre Hospitalier Creil France 60100
    10 Hôpital Henri Mondor (AP-HP) Créteil France 94000
    11 Centre hospitalier Dunkerque France 59240
    12 Centre Hospitalier Lens France 62300
    13 University hospital Lille France 59037
    14 Centre hospitalier Sambre en avesnois Maubeuge France 59600
    15 University hospital Montpellier France 34295
    16 University hospital Nantes France 45000
    17 University hospital Nice France 06202
    18 Hôpital Saint Antoine (AP-HP) Paris France 75012
    19 Hôpital de la Pitié-Salpétrière (AP-HP) Paris France 75013
    20 Hôpital Cochin (AH-HP) Paris France 75014
    21 University hospital Poitiers France 49000
    22 University hospital Rennes France 35033
    23 Centre Hospitalier Victor Provo Roubaix France 59100
    24 University Hospital Strasbourg France 67100
    25 Centre Hospitalier Tourcoing France 59208
    26 Centre Hospitalier Valenciennes France 59300
    27 University hospital, Nancy Vandoeuvre les nancy France 54511
    28 Hôpital Paul Brousse (AH-HP) Villejuif France 94000

    Sponsors and Collaborators

    • University Hospital, Lille
    • Ministry of Health, France

    Investigators

    • Principal Investigator: Philippe MATHURIN, MD PhD, University Hospital, Lille

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT01214226
    Other Study ID Numbers:
    • 2006-006944-78
    • PROM 2006/0636
    • 2006-006944-78
    First Posted:
    Oct 4, 2010
    Last Update Posted:
    Jun 1, 2011
    Last Verified:
    Sep 1, 2010
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis
    Liver Diseases
    Hepatitis, Alcoholic
    Liver Diseases, Alcoholic
    Pentoxifylline

    Study Results

    No Results Posted as of Jun 1, 2011