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

Hepatitis C, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00119119
• Other study ID #: ANRSHC10 PENTO
• Status: Terminated
• Phase: Phase 3
• First received: July 4, 2005
• Last updated: January 11, 2007
• Start date: February 2002
• Est. completion date: December 2006

Study information

• Verified date: January 2007
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Liver Fibrosis

Intervention

Drug:
• pentoxyphilline

• tocopherol

Locations

Country	Name	City	State
France	Service d'hepatologie Hopital Necker	Paris

Sponsors (1)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Variation of fibrosis Metavir score between the two biopsies
Secondary	Variation of activity Metavir score between the two biopsies
Secondary	Variation of liver markers of fibrosis : hyaluronate, N-terminal peptide of procollagen III, TNF-alfa and fibrotest
Secondary	Variation of ALT