Clinical Trial of Pentoxifylline in Patient With Cirrhosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cirrhosis, Liver Failure

Intervention / Treatment
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* Drug: pentoxifylline
* Drug: PLACEBO


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Patients with severe cirrhosis treated with Pentoxifylline | Drug: pentoxifylline<br>* Patients with severe cirrhosis treated with Pentoxifylline<br>|
| Placebo Comparator: 2<br>Patients with severe cirrhosis treated with a placebo | Drug: PLACEBO<br>* Patients with severe cirrhosis treated with a placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival rate at 2 months |  | at 2 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multicenter-randomized-trial, pentoxifyllinE, placebo, cirrhosis, liver failure, cytokine