Clinical trial NCT00162552: Clinical Trial of Pentoxifylline in Patient With Cirrhosis
Official title: Clinical Trial of Pentoxifylline Administration Versus Placebo on Survival in Patients With Cirrhosis and Severe Liver Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cirrhosis
Liver Failure
Keywords: multicenter-randomized-trial
pentoxifyllinE
placebo
cirrhosis
liver failure
cytokine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2005-09-13
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: survival rate at 2 months
timeFrame: at 2 months
Secondary outcomes:
measure: - survival rate at 6 months
timeFrame: at six months
measure: - Number of patient with liver transplantation
timeFrame: during the study
measure: - Complications : bacterial infection, renal insufficiency, hepatic encephalopathy, gastrointestinal bleeding
timeFrame: during the study
measure: - Fibrotest and Acutest before, at 2 months and at 6 months
timeFrame: at 2 months and at 6 months
measure: - TNF alpha and IL6 plasma concentration before, at 2 months and at 6 months as predictive factor of mortality
timeFrame: at 2 months and at 6 months as predictive factor of mortality
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
Study officials:
affiliation: hopital Beaujon, APHP, france
name: Didier LEBREC, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lebrec D, Thabut D, Oberti F, Perarnau JM, Condat B, Barraud H, Saliba F, Carbonell N, Renard P, Ramond MJ, Moreau R, Poynard T; Pentocir Group. Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis. Gastroenterology. 2010 May;138(5):1755-62. doi: 10.1053/j.gastro.2010.01.040. Epub 2010 Jan 25.