Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial

Publication

Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial

Journal Paper/Review - Jun 1, 2003

Berg Thomas, Hopf Uwe, Pape Gerd R, Wursthorn Karsten, Nasser Samer, Goeser Tobias, Spengler Ulrich, Herrmann Eva, Buggisch Peter, Gerlach Tilman, Hinrichsen Holger, Kronenberger Bernd, Zeuzem Stefan

Citation

Berg T, Hopf U, Pape G, Wursthorn K, Nasser S, Goeser T, Spengler U, Herrmann E, Buggisch P, Gerlach T, Hinrichsen H, Kronenberger B, Zeuzem S. Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial. Hepatology (Baltimore, Md.) 2003; 37:1359-67.

Type

Journal Paper/Review (English)

Journal

Hepatology (Baltimore, Md.) 2003; 37

Publication Date

Jun 1, 2003

Issn Print

0270-9139

Pages

1359-67

Brief description/objective

The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial. In this randomized, prospective, placebo-controlled, multicenter trial, triple therapy with interferon alfa (IFN-alpha)-2a plus ribavirin and amantadine (amantadine group) was compared with combination therapy IFN-alpha plus ribavirin (control group). Four hundred previously untreated patients with histologically proven chronic hepatitis C were randomly allocated to treatment with amantadine sulphate (100 mg twice daily orally) or a matched placebo together with IFN-alpha induction plus ribavirin (1,000-1,200 mg/day orally) for 48 weeks. The primary end point was sustained virologic response (SVR) defined as undetectable serum hepatitis C virus (HCV) RNA (<100 copies/mL) 24 weeks after the end of treatment. SVR was observed in 52% of the amantadine group and in 43.5% of the control group (P =.11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively. The virologic on-treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group (70% vs. 59%, respectively, P =.016). This beneficial effect was mainly related to HCV type 1-infected patients (63% vs. 47%, respectively, P =.012). Independent factors associated with SVR, according to multiple logistic regression analysis, were amantadine treatment, low baseline HCV RNA, platelet counts (>/=250/nL), pretreatment ALT quotient >/=3, and GGT level (<28 U/L) as well as HCV genotypes other than 1. In conclusion, although we could not demonstrate a significant advantage of the triple regimen in univariate analysis, multivariate analysis offers arguments that amantadine should be considered as a potential anti-HCV drug in future studies.