Clinical trial NCT00119119: Efficacy and Safety of Pentoxyphilline and Tocopherol on the Fibrosis in Patients With Chronic Hepatitis C
Official title: Efficacy and Safety of the Association With Pentoxyphilline and Tocopherol on the Fibrosis in Patients With Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Liver Fibrosis
Keywords: Hepatitis C
Liver Cirrhosis
Tocopherols
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-07-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The fibrosis of liver is a complication of chronic hepatitis C. There is actually no established treatment for fibrosis of the liver. Pentoxyphilline and tocopherol may have an activity on fibrosis. The aim of the study is to analyse the efficacy and the safety of the combination with pentoxyphilline and tocopherol (12 months) on liver fibrosis, in patients with chronic hepatitis C, who are non-long-term responders, or with intolerance or contra-indication to interferon-alfa and ribavirin.

Detailed description: The aim of this study is to analyse the efficacy and the safety of the combination of pentoxyphilline (400 mg, twice a day) and tocopherol (500 mg, twice a day), given during 12 months on the fibrosis related to HCV chronic hepatitis in 100 patients who are non-long-term responders, or with contra-indication or intolerance to the current treatment of reference (combination with interferon-alfa and ribavirin). It is a therapeutic, national, multicentric, double-blind, placebo-controlled phase III trial. The patients included had histological liver injuries with a Metavir score of A 0 to 2, F 2 or 3 and no other etiology of liver disease. The primary objective is to analyse the variation of the liver fibrosis evaluated by morphometric analysis between the 2 liver biopsies performed at the end of the trial and within 3 years before the treatment. The secondary objectives are the variation of the Metavir fibrosis and activity scores, of serum markers of fibrosis (hyaluronate, PIIIP, TNF-alfa, fibrotest) and ALT between the end and the beginning of the treatment.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 75 years
* Chronic hepatitis C defined by positive HCV Ab and HCV RNA and histological proven injuries
* Liver biopsy with a size over or equal to 15mm, performed within 3 years of enrolment, with a Metavir score of activity from 0 to 2 and fibrosis score of 2 or 3.
* Non long term responders or patients with contra-indication or intolerance to interferon alfa or ribavirin
* No anti-viral treatment during the trial
* Signed written informed consent

Exclusion Criteria:

* Alcohol consumption over or equal to 40 g/d
* Allergy to tocopherol or pentoxyphilline
* Treatment with platelet anti-aggregates, anti-vitamin K, theophylline, armophylline
* Treatment with tocopherol or pentoxyphilline since the last liver biopsy
* Pregnancy, breast feeding, lack of contraception
* Decompensated cirrhosis, organ graft, chronic renal insufficiency
* BMI over 27
* Diabetes type I or II
* Other etiology of liver disease (HBV, HIV, hemochromatosis, alfa-1 antitrypsin deficiency, Wilson's disease, auto-immune hepatitis, drug-related hepatitis)

Primary outcomes:
measure: Variation of the percentage of liver fibrosis evaluated with morphometric analysis between the liver biopsies performed at the end and before the trial (defined as significant if over 5 percent).
Secondary outcomes:
measure: Variation of fibrosis Metavir score between the two biopsies
measure: Variation of activity Metavir score between the two biopsies
measure: Variation of liver markers of fibrosis : hyaluronate, N-terminal peptide of procollagen III, TNF-alfa and fibrotest
measure: Variation of ALT
Other outcomes:
Locations:
city: Paris
country: France
facility: Service d'hepatologie Hopital Necker
Study officials:
affiliation: Service d'hepatologie Hopital Necker Paris
name: Helene Fontaine, MD
role: PRINCIPAL_INVESTIGATOR
References: