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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].

Veldt BJ, Brouwer JT, Adler M, Nevens F, Michielsen P, Delwaide J, Hansen BE, Schalm SW, Benelux Study Group on Treatment of Chronic Hepatitis - BMC Gastroenterol (2003)

Bottom Line: One patient did not fit the entry criteria, and 3 did not start.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterology of the Erasmus Medical Center Rotterdam, The Netherlands. b.veldt@erasmusmc.nl

ABSTRACT

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 until 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 x 10(6) 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.

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Related in: MedlinePlus

Cumulative probability of ALT response during treatment. Patients treated with combination therapy in this trial vs results of the same patients in a previous trial with interferon monotherapy [4]. There is a trend towards increased normalisation rate with interferon and ribavirin combination therapy.
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Figure 4: Cumulative probability of ALT response during treatment. Patients treated with combination therapy in this trial vs results of the same patients in a previous trial with interferon monotherapy [4]. There is a trend towards increased normalisation rate with interferon and ribavirin combination therapy.

Mentions: Figure 4 shows the rates of ALT normalisation of 26 patients who were treated in a previous trial with interferon monotherapy [4] compared to the rates of ALT normalisation the same patients showed in this trial on combination therapy. There is a trend towards increased ALT normalisation rate with interferon and ribavirin combination therapy.


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].

Veldt BJ, Brouwer JT, Adler M, Nevens F, Michielsen P, Delwaide J, Hansen BE, Schalm SW, Benelux Study Group on Treatment of Chronic Hepatitis - BMC Gastroenterol (2003)

Cumulative probability of ALT response during treatment. Patients treated with combination therapy in this trial vs results of the same patients in a previous trial with interferon monotherapy [4]. There is a trend towards increased normalisation rate with interferon and ribavirin combination therapy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC222984&req=5

Figure 4: Cumulative probability of ALT response during treatment. Patients treated with combination therapy in this trial vs results of the same patients in a previous trial with interferon monotherapy [4]. There is a trend towards increased normalisation rate with interferon and ribavirin combination therapy.
Mentions: Figure 4 shows the rates of ALT normalisation of 26 patients who were treated in a previous trial with interferon monotherapy [4] compared to the rates of ALT normalisation the same patients showed in this trial on combination therapy. There is a trend towards increased ALT normalisation rate with interferon and ribavirin combination therapy.

Bottom Line: One patient did not fit the entry criteria, and 3 did not start.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterology of the Erasmus Medical Center Rotterdam, The Netherlands. b.veldt@erasmusmc.nl

ABSTRACT

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 until 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 x 10(6) 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.

Show MeSH
Related in: MedlinePlus