Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C
- P J Thuluvath1,
- A Maheshwari1,
- J Mehdi1,
- K D Fairbanks1,
- L L-W Wu1,
- L G Gelrud2,
- M J Ryan3,
- F A Anania4,
- I F Lobis2,
- M Black5
- 1Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
- 2Hopkins Hepatology HCV Research Group, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
- 3Eastern Virginia Medical School, Norfolk, VA, USA
- 4University of Maryland, Baltimore, MD, USA
- 5Temple University, Philadelphia, PA, USA
- Correspondence to:
Dr P J Thuluvath
Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, 1830 E Monument Street, Suite 429, Baltimore, MD 21205, USA;
- Accepted 19 August 2003
Background and aim: In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment naïve patients with chronic hepatitis C virus (HCV).
Methods: In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000–1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment.
Results: At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p = 0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects.
Conclusion: Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.
- HCV, hepatitis C virus
- SVR, sustained virological response
- PCR, polymerase chain reaction
- ALT, alanine aminotransferase
- TSH, thyroid stimulating hormone