Purpose / DescriptionThis randomized controlled trial examined the efficacy and safety of combination therapy with peginterferon alfa-2a plus ribavirin compared with peginterferon alfa-2a plus placebo (monotherapy) or standard interferon alfa-2a plus ribavirin. A total of 1,121  treatment-naïve patients with chronic hepatitis C were enrolled in the trial. Sustained virologic response (SVR) rate at 24 weeks post-treatment was greater among patients who received peginterferon alfa-2a  plus ribavirin than with either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy (56% versus 44% and 29% respectively, p<0.001). Independent predictors of SVR in this study included genotypes other than genotype 1, age less than 40 years, and body weight of 75 kg or less. The overall side effect profiles were similar between the three treatment arms. This study clearly established that (1) peginteferon alfa-2a and ribavirin was superior to standard interferon alfa-2a and ribavirin, and (2) the addition of ribavirin to peginterferon alfa-2a significantly improves SVR rates.