Although the antiviral effects of amantadine sulphate (1-aminoadamantan sulphate) have not been characterized for the hepatitis C virus (HCV), previous pilot studies have suggested promising results in patients with chronic hepatitis C. The aim of the present study was to compare the efficacy, safety, and health-related quality of life (HRQOL) of interferon alfa (IFN-␣) alone or in combination with oral amantadine for treatment of chronic hepatitis C. One hundred nineteen previously untreated patients with chronic hepatitis C were randomly allocated to treatment with IFN␣2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks, followed by 3 megaunits 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. Hepatitis C virus (HCV) infection often progresses to chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma. 1 Chronic hepatitis C infection is a leading cause of chronic liver disease and the most common indication for liver transplantation. Treatment of HCV-infected patients with interferon alfa (IFN-␣) can achieve viral clearance and improve histology and prognosis. However, the overall sustained virologic response to IFN-␣ monotherapy is less than 20%. 2,3 Recent studies investigating the efficacy of combination therapy with IFN-␣ and ribavirin in patients with chronic hepatitis C, showed improved sustained virologic response rates of approximately 40%. 4,5 Nevertheless, further improvements in the treatment of chronic hepatitis C are still needed.Amantadine (1-aminoadamantan) is a tricyclic amine with antiviral activity against toga-, myxo-, arena-, flavi-, and coronaviruses. 6-10 Inhibition of influenza A virus replication by amantadine is clinically well characterized. 11 The molecular mechanisms include inhibition of an early step in viral replication, most likely viral uncoating and interaction with the viral M2 protein, which is a membrane-bound protein thought to be important in virus budding. 12,13 Although antiviral effects of amantadine have not been characterized for the hepatitis C virus, promising results have been reported in several pilot studies of HCV-infected patients treated with amantadine alone [14][15][16] or in combination with IFN-␣. 15,17 The aim of this study was to compare efficacy, safety, and health-related quality of life (HRQOL) of therapy with IFN␣2a alone and in combination with oral amantadine sulphate, administered for 48 weeks for the treatment of chronic HCV infection in patients who have not previously been treated with IFN, ribavirin, and/or amantadine.
PATIENTS AND METHODSPatients. Men and women aged 18 to 70 years with compensated chronic HCV infection not previously treated with IFN, ribavirin, and/or amantadine were eligible for enrollment. Eligible patients tested positive for anti-HCV (second-generation enzyme immunoassay) and HCV ...