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

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by:
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01214226
First received: October 1, 2010
Last updated: May 31, 2011
Last verified: September 2010
  Purpose

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 Intervention Phase
Alcoholic Hepatitis
Alcoholic Liver Disease
Drug: Pentoxifylline
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hepatorenal syndrome [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Score of Lille model [ Time Frame: Seven days ] [ Designated as safety issue: No ]
  • Percentage of Meld score (Model for End-stage Liver Disease) higher than 17 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 278
Study Start Date: December 2007
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01214226

Locations
Belgium
University hospital
Brussel, Belgium, 1070
France
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
Investigators
Principal Investigator: Philippe MATHURIN, MD PhD University Hospital, Lille
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Service des Maladies de l'Appareil Digestif, Hôpital Huriez,, CHRU Lille, France (Pr Philippe Mathurin / MD, PhD)
ClinicalTrials.gov Identifier: NCT01214226     History of Changes
Other Study ID Numbers: 2006-006944-78, PROM 2006/0636, 2006-006944-78
Study First Received: October 1, 2010
Last Updated: May 31, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Alcoholic
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
Pentoxifylline
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014