Randomized controlled trial of interferon gamma versus amantadine in combination with interferon alpha and ribavirin for hepatitis C genotype 3 non-responders and relapsers.

OBJECTIVES To evaluate the efficacy and safety of triple combination regimens comprising of interferon alpha-2b (IFN-alpha) and ribavirin plus either IFN-gamma or amantadine in genotype 3 patients, responders or relapsers to interferon plus ribavirin combination. METHODS Patients were randomized to receive IFN-alpha 3MU thrice a week, ribavirin 800-1200 mg per day with either IFN-gamma 2 MU thrice a week or amantadine 100 mg twice daily. Treatment was continued for 48 weeks in patients showing complete or partial (2 log reduction) early virological response (EVR) at 12 weeks and negative PCR at 24 weeks. RESULTS Total enrollments were 44; 25 were previously non-responders out of them 12 were in the IFN-gamma arm. Nineteen were relapsers, out of them 10 received IFN-Gamma. Overall EVR with triple regimens was 61.4% (27/44). The EVR for IFN-gamma arm was 72.7% (16/22) and for amantadine arm 50% (11/22) (p=0.089). Sustained virological response (SVR) was 50% (11/22) in the gamma arm and 27.3% (6/22) in the amantadine arm (p=0.122). This figure was 60% (6/10) and 44% (5/9) for relapsers (p=0.845), and 41.6% (5/12) and 7.7% (1/13) for non-responders (p = 0.046).Treatment was well tolerated by most of the patients in both arms. CONCLUSIONS About one third of patients responded to the triple regimens. However IFN-gamma was a better option. Its combination with pegylated interferon and ribavirin needs further evaluation. ( TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT00538811).