Efficacy and Safety of Pentoxyphilline and Tocopherol on the Fibrosis in Patients With Chronic Hepatitis C

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis (Other)

Overall Status

Terminated

CT.gov ID

NCT00119119

Collaborator

(none)

100

Enrollment

Location

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic Liver Fibrosis	Drug: pentoxyphilline Drug: tocopherol	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of the Association With Pentoxyphilline and Tocopherol on the Fibrosis in Patients With Chronic Hepatitis C

Study Start Date :

Feb 1, 2002

Study Completion Date :

Dec 1, 2006

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Variation of fibrosis Metavir score between the two biopsies []
Variation of activity Metavir score between the two biopsies []
Variation of liver markers of fibrosis : hyaluronate, N-terminal peptide of procollagen III, TNF-alfa and fibrotest []
Variation of ALT []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)