Randomized, double-blind, placebo-controlled trial of interferon Alfa2a with and without amantadine as initial treatment for chronic hepatitis C

Although the antiviral effects of amantadine sulphate (1-aminoadamantan sul phate) have not been characterized for the hepatitis C virus (HCV), previou s pilot studies have suggested promising results in patients with chronic h epatitis C, The aim of the present study was to compare the efficacy, safet y, and health-related quality of life (HRQOL) of interferon alfa (IFN-alpha ) alone or in combination with oral amantadine for treatment of chronic hep atitis C, One hundred nineteen previously untreated patients with chronic h epatitis C were randomly allocated to treatment with IFN-alpha 2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks, followed by 3 m egaunits thrice weekly for an additional 24 weeks plus amantadine sulphate administered orally 100 mg twice a day for 48 weeks or the same IFN regimen plus a matched placebo. The primary endpoint was undectable serum HCV RNA (< 1,000 copies/mL) at week 24 after treatment. At the end of treatment and the 24-week follow-up period serum HCV RNA was undetectable in 20 (34%) an d 6 (10%) of the 59 patients treated with the combination IFN-alpha plus am antadine and in 20 (33%) and 13 (22%) of the 60 patients treated with IFN-a lpha alone, respectively (P = n.s.), Discontinuation of therapy for adverse events was similar in both treatment groups. Although treatment with IFN-a lpha worsened HRQOL, combination with amantadine showed a substantial trend to improve fatigue and vigor. In conclusion, combination therapy IFN-alpha plus amantadine is as effective as IFN-alpha monotherapy in previously unt reated patients with chronic hepatitis C.