Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378]

BMC Gastroenterology

Solko W Schalm²  Bettina E Hansen⁷  Jean Delwaide⁴  Peter Michielsen¹  Frederik Nevens³  Michael Adler⁵  Johannes T Brouwer⁶  Bart J Veldt² 

[1] Departments of Gastroenterology and Hepatology of the University Hospital Antwerp, Belgium;Departments of Gastroenterology and Hepatology of the Erasmus Medical Center Rotterdam, the Netherlands;Departments of Gastroenterology and Hepatology of the University Hospital Leuven, Belgium;Departments of Gastroenterology and Hepatology of the University Hospital Liège, Belgium;Departments of Gastroenterology and Hepatology of the Erasme University Hospital Brussels, Belgium;Departments of Gastroenterology and Hepatology of the Reinier de Graaf Hospital Group Delft, the Netherlands;Department of Biostatistics, Erasmus Medical Center Rotterdam, the Netherlands

关键词: Placebo;    Monotherapy;    Non-responders;    Ribavirin;    Interferon;    Randomised controlled trial;    Treatment;    Hepatitis C;   

Others  :  1215878
DOI  :  10.1186/1471-230X-3-24

 received in 2003-06-02, accepted in 2003-08-29,  发布年份 2003

【 摘 要 】

Background

Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now.

Methods

One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 × 10⁶ copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000–1200 mg / day), 6 months ribavirin monotherapy (1000–1200 mg / day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis.

Results

At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin.

During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01).

Discussion

This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts.

【 授权许可】

   
2003 Veldt et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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