Interim analysis of a randomized controlled trial of combination of ribavirin and high dose interferon-alpha in interferon nonresponders with chronichepatitis C

This trial investigated the efficacy of a combination of high-dose interfer on-alpha (IFN-alpha) with ribavirin in IFN nonresponders. Study protocol: 3 04 patients with chronic hepatitis C were treated with 5 MU IFN-alpha 2b (I ntronA(R), Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW fo r each 3 months) alone (group A) or in combination with ribavirin (1-1.2 g per day) (group B), ALT was measured in monthly intervals, HCV-RNA in 3 mon thly intervals, Pretreatment characteristics of the randomized patients wer e as follows: group A, n = 76: m/f, 54/22; 16% cirrhosis, age, 45.7 +/- 12 years; ALT (U per litre), 66 +/- 35; group B, 81; m/f, 57/24: 17% cirrhosis , age, 48.2 +/- 12: ALT, 71 +/- 40, After 9 months of treatment, nine (11.6 %) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop- outs in group A and 15 in group B, Six months after treatment only two pati ents in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT an d no detectable HCV-RNA in serum, In addition to the well-known side-effect s of IFN the mean haemoglobin concentration dropped by 2 g per litre in gro up B, These data indicate that a combination of high-dose IFN with ribaviri n is effective in inducing a short-lasting complete response in one-third o f IFN nonresponders, Prolonged treatment with IFN/ribavirin may be necessar y to obtain a sustained response.