Rationale and design of TeraViC-4 study: A phase III, randomized clinical trial to evaluate the effects of treatment duration with peginterferon alfa-2a (40-kDa) and ribavirin in naive patients with chronic hepatitis C virus infection without early virological response at week 4

Several studies are available on the efficacy and safety of 40 kDa branched peginterferon alfa-2a (40-kDa) combined with ribavirin in the treatment of chronic hepatitis C patients. The TeraViC-4 study is a phase III. randomized, parallel group, multicenter study that includes two additional open arms. The main objective is to investigate if extended therapy over 72 weeks increases the rate of sustained virological response induced by il standard 48-week treatment period in naive patients with chronic hepatitis C who do not show an early virological response. All patients will be treated with peginterferon alfa-2a (40-kDa), 180 μg subcutaneous (s.c.) once-weekly, and ribavirin, 400 mg b.i.d. Virological response will be assessed by a hepatitis C virus ribonucleic acid (HCV-RNA) qualitative palymerase chain reaction (PCR) test. Non-early responders (HCV-RNA still detectable after 4 weeks of therapy) will be randomly separated to receive combination therapy for 44 or 68 additional weeks. Early responders (undetectable HCV-RNA at week 4) will be allocated into two open arms according to HCV genotype and basal viral load, and they will be treated for 20 or 44 additional weeks. All patients will be followed for 24 weeks on no therapy. A total of 504 patients are planned to be included in the study in order to reach the required sample size in the two randomized groups. Efficacy of treatment will be assessed by determination of HCV-RNA and the primary efficacy variable is the rate of sustained virological response (after 24 weeks of treatment-free follow-up) in patients without early virological response. Secondary efficary variables are the rate of sustained biochemical response, the rate of response in function of HCV genotype, viral load and treatment duration. Safety data will also be recorded and analyzed.