Cirrhosis, Liver Failure
Conditions
Keywords
multicenter-randomized-trial, pentoxifyllinE, placebo, cirrhosis, liver failure, cytokine
Brief summary
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
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.
Interventions
DRUGpentoxifylline
Patients with severe cirrhosis treated with Pentoxifylline
DRUGPLACEBO
Patients with severe cirrhosis treated with a placebo
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| survival rate at 2 months | at 2 months |
Secondary
| Measure | 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 |
Countries
France
Outcome results
None listed