Study on Chronic Hepatitis C Treatment With Interferon Alpha, Ribavirin and Amantadine in Naive Patients

The CIRA-study is a double blind, placebo controlled, randomised, multicentre study in previously untreated patients suffering from chronic hepatitis C comparing double therapy, consisting of (PEG-)interferon alpha 2b ((PEG)Intron-A®) and ribavirin (Rebetol®), with triple therapy, consisting of (PEG-)interferon alpha 2b, ribavirin and amantadine, for 52 weeks. Follow-up is completed at week 104. 150 Subjects per treatment group will be included. Patients will be stratified before randomisation according to genotype (1 versus non-1). Viral load will not be a discriminating factor.

The aim is to investigate the efficacy of the adjunct amantadine to the currently used combination therapy with interferon alpha and ribavirin.

Inclusion criteria

• Anti-HCV positivity >6 months
• ALT and/or AST elevation on at least once in the previous 6 months
• Positive HCV-RNA
• Liver biopsy within one year before the start of therapy in non- cirrhosis. In the case of known cirrhosis, liver biopsy is not necessary
• Intention to be treated and participate treatment
• Obtained written informed consent

Exclusion criteria

• Age < 18 years
• Pregnancy or intention to get pregnant within the 12 months period of treatment and up to 6 months after discontinuation of therapy, no adequate contraception, lactation
• Men not practicing or willing to practice acceptable methods of contraception during the treatment period and up to 6 months after discontinuation of therapy
• Life expectancy < 1 year
• Child Pugh B or C (Appendix III)
• Creatinine > 150 μmol/L or > 1.70 mg/dl
• Haemoglobulin < 6.5 mmol/l or < 10.5 g/dl
• White blood cell count < 2,5 x 109/L, neutrophil < 1,5 x 109/L
• Platelet count < 70 x 109/L
• HIV positivity
• Chemotherapy, systematical antiviral treatment during the 6 months prior to study entry
• Other serious disease (e.g. malignancy, uncontrolled myocardial disease or severe arrhythmias)
• Active uncontrolled psychiatric disorders and suicidal leanings
• Patients with a history of uncontrolled seizure or other significant CNS dysfunction
• Any condition which in the opinion of the (co-)investigator might interfere with the evaluation of the study objectives