Official Title: “Clinical Trial of Pentoxifylline Administration Versus Placebo on Survival in Patients With Cirrhosis and Severe Liver Failure”

In patients with cirrhosis and liver failure, pro-inflammatory cytokines (TNF alpha) might be responsible of severe complications and death. Thus, the prevention of cytokine production should prevent complications and mortality. The aim of this study is to study the 2 months survival rate in patients with severe cirrhosis (Child-Pugh C) with pentoxifylline - an inhibitor of cytokine production. The 6 month mortality, the proportion of transplanted patients, the occurrence of complications (bacterial infection, renal failure, hepatic encephalopathy and gastrointestinal bleeding), plasma cytokine levels and fibrotest - a marker of fibrosis - will be also studied. This is a multicenter double blind randomized trial with a placebo. All adult patients with severe cirrhosis might be randomized after written consent. Patients with severe carcinoma, intolerance or contraindication to pentoxifylline will not be included. Patients receive either pentoxifylline or placebo 3 times a day for 6 months. Three hundred and forty two patients are necessary to decrease mortality rate by 50% at 2 months in a beta risk of 10% and an alpha risk of 5%. Patients will be seen every month.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2007

The aim of this study is to study the 2 months survival rate in patients with severe cirrhosis (Child-Pugh C) with pentoxifylline - an inhibitor of cytokine production. The 6 month mortality, the proportion of transplanted patients, the occurrence of complications (bacterial infection, renal failure, hepatic encephalopathy and gastrointestinal bleeding), plasma cytokine levels and fibrotest - a marker of fibrosis - will be also studied. This is a multicenter double blind randomized trial with a placebo. All adult patients with severe cirrhosis might be randomized after written consent. Patients with severe carcinoma, intolerance or contraindication to pentoxifylline will not be included. Patients receive either pentoxifylline or placebo 3 times a day for 6 months. Three hundred and forty two patients are necessary to decrease mortality rate by 50% at 2 months in a beta risk of 10% and an alpha risk of 5%. Patients will be seen every month.

Intervention(s) in this Clinical Trial

• Drug: pentoxifylline
  • Patients with severe cirrhosis treated with Pentoxifylline
• Drug: PLACEBO
  • Patients with severe cirrhosis treated with a placebo

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Patients with severe cirrhosis treated with Pentoxifylline
• Placebo Comparator: 2
  • Patients with severe cirrhosis treated with a placebo

Primary Measures

• survival rate at 2 months
  • Time Frame: at 2 months
    Safety Issue?: Yes

Secondary Measures

• - survival rate at 6 months
  • Time Frame: at six months
    Safety Issue?: Yes
• - Number of patient with liver transplantation
  • Time Frame: during the study
    Safety Issue?: Yes
• - Complications : bacterial infection, renal insufficiency, hepatic encephalopathy, gastrointestinal bleeding
  • Time Frame: during the study
    Safety Issue?: Yes
• - Fibrotest and Acutest before, at 2 months and at 6 months
  • Time Frame: at 2 months and at 6 months
    Safety Issue?: Yes
• - TNF alpha and IL6 plasma concentration before, at 2 months and at 6 months as predictive factor of mortality
  • Time Frame: at 2 months and at 6 months as predictive factor of mortality
    Safety Issue?: Yes

Inclusion Criteria:

• adult patient of more than 18 years
• child pugh C cirrhosis

Exclusion Criteria:

• pregnant woman
• Patient received anticoagulant
• Patient treated for arterial hypertension
• Patient with severe coronaropathy
• Patient with hyper sensibility of pentoxifylline
• Patient hospitalized for less 24 hours
• Patient admitted for a treatment of hepatocellular-carcinoma or COLLANGIO- carcinoma
• Patient with HIV
• Patient who has been transplanted
• Patient treated with immuno- suppressors
• Patient who has already received pentoxifylline for 3 months before inclusion
• Patient for whom the follow-up is considered impossible

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

Didier LEBREC, MD Principal Investigator hopital Beaujon, APHP, france  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00162552

Study ID Number: P030439

ClinicalTrials.gov Identifier: NCT00162552

Health Authority: France: Ministry of Health