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

✍ Scribed by Michael von Wagner; Wolf Peter Hofmann; Gerlinde Teuber; Thomas Berg; Tobias Goeser; Ulrich Spengler; Holger Hinrichsen; Hans Weidenbach; Guido Gerken; Michael Manns; Peter Buggisch; Eva Herrmann; Stefan Zeuzem

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 134 KB
• Volume: 48
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22483

✦ Synopsis

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 g 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.