Clinical trial NCT00927290: Pioglitazone vs. Placebo in Association With Pegylated Interferon and Ribavirin in HCV Patients With Insulin Resistance
Official title: ANRS HC 22, PEGLIST-C, Multicenter, Randomized Controlled Trial of Pioglitazone vs. Placebo in Association With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C, Non 2 or 3 Genotypes and Insulin Resistance
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Hepatitis C
Insulin Resistance
Keywords: hepatitis C; insulin resistance; glitazones; pioglitazone; steatosis; viral kinetics; antiviral response
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2009-06-24
Enrollment: 40
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: The purpose of this study is to test whether the correction of insulin resistance with pioglitazone, will improve the response to antiviral treatment.

Detailed description: In patients infected with genotypes 1, 4, 5 and 6, the response rate to antiviral therapy remains suboptimal (less than one in two patients have a sustained virological response), which justifies the search for strategies optimizing the results of antiviral therapy. Some factors associated with non response have been identified. Among the modifiable factors, numerous series have shown that insulin resistance adversely impacts the rate of sustained virological response. The aim of this study is to determine whether the pharmacological correction of insulin resistance through therapy with glitazones restores higher rates of viral eradication and to determine the impact on the kinetics of viral response. Patients will be randomized to receive pioglitazone or placebo starting 4 months before initiating pegylated interferon and ribavirin and continued throughout the whole antiviral treatment period.

Eligibility criteria: Inclusion Criteria:

* 18 years old or older
* Chronic HCV infection documented by PCR with genotype HCV-1, 4, 5 or 6
* Naive Patient(never treated with antivirals for HCV)
* HOMA score higher than 2.5
* Patient for which the investigator decided to start antiviral treatment for chronic hepatitis C

Exclusion Criteria:

* Cardiovascular disease: heart failure stage NYHA II, III or IV, unstable angina, myocardial infarction in the previous year, cardiac surgery or stroke
* Alcohol consumption exceeding 40 g / day
* Decompensated liver disease: Child-Pugh B 8 or higher, or one of the following : bilirubin over 35 mol / L, TP below 50%, ascites, encephalopathy
* Hepatocellular carcinoma or any other neoplasm (except if in remission for \> 5 years)
* Other documented chronic liver disease
* Insulin treated diabetes
* HBV or HIV co-infection infection confirmed
* Thrombocytopenia below 50 000/mm ³; neutropenia below 750/mm ³ or hemoglobin below 11 g / dL
* Drug-induced steatosis(tamoxifen, glucocorticosteroids, amiodarone, tetracyclines).
* Bone marrow or solid organ transplantation
* Pregnancy or breastfeeding, or desire for pregnancy during the study period.
* Patients under legal protection or unable to express their consent

Primary outcomes:
measure: Decrease in the HOMA score below 2 after 4 months of treatment with pioglitazone or placebo(at W16). The efficiency is defined as a higher proportion of subjects with HOMA <2 in the pioglitazone group than in the group treated with placebo pioglitazone.
timeFrame: W16
Secondary outcomes:
measure: Kinetics of decrease in viral response to pegylated interferon. Early virological response rates. Rates of sustained virological response. Effect on steatosis
timeFrame: EVR at W16 and W28 SVR at W88
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière, Service d'hépatogastroentérologie
Study officials:
affiliation: Hôpital Pitié--Salpêtrière, 83 Bd de l'Hôpital 75651 Paris cedex 13, FRANCE
name: Vlad RATZIU, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: