Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection

Authors


  • Presented in part at the 58th Annual Meeting of the American Association for the Study of Liver Diseases, November 2-6, 2007, Boston, MA.

  • Potential conflict of interest: Dr. Teuber advises, is on the speakers' bureau of, and received grants from Essex Pharma. She is on the speakers' bureau of and received grants from Roche Pharma. She is also on the speakers' bureau of Gilead and Bristol-Myers Squibb. Drs. Berg and Spengler are on the speakers' bureau of, and received grants from Roche. Dr. Buggisch is on the speakers' bureau of Roche. Dr. Zeuzem is a consultant for and is on the speakers' bureau of Roche and Schering-Plough. He is on the speakers' bureau of Merz.

Abstract

The impact of amantadine on virologic response rates of interferon-based treatment of chronic hepatitis C is controversial. The aim of this study was to compare virological response rates in patients with chronic hepatitis C virus (HCV)-1 infection treated with 400 mg amantadine or placebo in combination with peginterferon alfa-2a (40 kD) and ribavirin for 48 weeks. Seven hundred four previously untreated chronically HCV-1–infected patients (mean age, 46 ± 12 years) were randomized to (A) amantadine-sulphate (400 mg/day) (n = 352) or (B) placebo (n = 352), both in combination with 180 μg peginterferon alfa-2a once weekly and ribavirin (1000-1200 mg/day) for 48 weeks. End of treatment and sustained virological response after a 24-week follow-up period were assessed by qualitative reverse transcription polymerase chain reaction (RT-PCR) (sensitivity, 50 IU/mL). Demographic and baseline virological parameters were similar in both treatment groups. In groups A and B, 231 of 352 patients (66%) and 256 of 352 patients (72%) achieved an end of treatment response, and 171 of 352 patients (49 %) and 186 of 352 patients (53 %) a sustained virological response, respectively. On-treatment dropout rate in the amantadine group was significantly higher than in the placebo group (32% versus 23%; P = 0.01). However, adverse events and laboratory abnormalities were similar between both groups. Per-protocol analysis revealed similar sustained virological response rates in both treatment groups (53% versus 55%). Conclusion: In this large placebo-controlled multicenter study, amantadine even at a dose of 400 mg/day did not improve virological response rates of peginterferon alfa-2a and ribavirin in patients with chronic genotype HCV-1 infection. (HEPATOLOGY 2008.)

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