Double-blind Randomized Controlled Trial in Severe Alcoholic Hepatitis (CorpentoxHAA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01214226
Recruitment Status : Completed
First Posted : October 4, 2010
Last Update Posted : June 1, 2011
Ministry of Health, France
Information provided by:
University Hospital, Lille

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
Alcoholic Hepatitis Alcoholic Liver Disease Drug: Pentoxifylline Drug: placebo 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 Type : Interventional  (Clinical Trial)
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 : December 2007
Actual Primary Completion Date : December 2010
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

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 Name: TORENTAL 400MG

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Hepatorenal syndrome [ Time Frame: 6 months ]
  2. Score of Lille model [ Time Frame: Seven days ]
  3. Percentage of Meld score (Model for End-stage Liver Disease) higher than 17 [ Time Frame: 6 months ]

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01214226

University hospital
Brussel, Belgium, 1070
University hospital
Angers, France, 49933
Hôpital Jean Verdier (AH-HP)
Bondy, France, 93143
University hospital
Bordeaux, France, 33000
Centre hospitalier
Béthune, France, 62408
University hospital
Caen, France, 14000
Hospital Antoine Béclère (Assistance Publique des Hôpiaux de Paris)
Clamart, France, 92141
Hôpital Beaujon (AH-HP)
Clichy, France, 92118
Centre Hospitalier
Creil, France, 60100
Hôpital Henri Mondor (AP-HP)
Créteil, France, 94000
Centre hospitalier
Dunkerque, France, 59240
Centre Hospitalier
Lens, France, 62300
University hospital
Lille, France, 59037
Centre hospitalier Sambre en avesnois
Maubeuge, France, 59600
University hospital
Montpellier, France, 34295
University hospital
Nantes, France, 45000
University hospital
Nice, France, 06202
Hôpital Saint Antoine (AP-HP)
Paris, France, 75012
Hôpital de la Pitié-Salpétrière (AP-HP)
Paris, France, 75013
Hôpital Cochin (AH-HP)
Paris, France, 75014
University hospital
Poitiers, France, 49000
University hospital
Rennes, France, 35033
Centre Hospitalier Victor Provo
Roubaix, France, 59100
University Hospital
Strasbourg, France, 67100
Centre Hospitalier
Tourcoing, France, 59208
Centre Hospitalier
Valenciennes, France, 59300
University hospital, Nancy
Vandoeuvre les nancy, France, 54511
Hôpital Paul Brousse (AH-HP)
Villejuif, France, 94000
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Principal Investigator: Philippe MATHURIN, MD PhD University Hospital, Lille

Publications of Results:

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Service des Maladies de l'Appareil Digestif, Hôpital Huriez,, CHRU Lille, France (Pr Philippe Mathurin / MD, PhD) Identifier: NCT01214226     History of Changes
Other Study ID Numbers: 2006-006944-78
PROM 2006/0636 ( Other Identifier: CHRU de Lille - promoteur )
2006-006944-78 ( EudraCT Number )
First Posted: October 4, 2010    Key Record Dates
Last Update Posted: June 1, 2011
Last Verified: September 2010

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis A
Liver Diseases
Liver Diseases, Alcoholic
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents