Retreatment With High Doses of pegIFN Alfa-2a and Ribavirin of Previous Nonresponders HIV-coinfected Patients With Cirrhosis Due to HCV 1-4
Objective: To evaluate the efficacy and safety of high doses of both peginterferon-alfa 2a (360 ug per week) plus ribavirin (800 mg b.i.d.) in HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(*) to a standard dose treatment of both drugs.
(*) Non previous virological response: no decrease of plasma RNA-HCV at least 2 log10 after 12 weeks in treatment or breakthrough viremia while on treatment.
Additionally, this study will evaluated the influence of simultaneous peginterferon-alfa 2a and ribavirin plasma concentrations on early viral response (EVR) and sustained viral response (SVR) in these patients.
Method: Pilot clinical trial, phase II-III, open labeled multicenter in which patients from several hospitals of the Servicio Andaluz de Salud will be enrolled.
The usual clinical and analytical follow up will be performed but additional blood samples will be obtained for determination of interferon and ribavirin plasma levels. The primary end point will be a sustained virologic response (defined as an undetectable serum HCV-RNA after 24 weeks after the cessation of treatment). Likewise, rapid virological response (at 4 weeks of treatment), early virological response (at 12 weeks), and end of treatment response rates will be evaluated as well as their relationships with the plasma interferon an ribavirin concentrations determined by ELISA and HPLC, respectively. The safety and tolerability of the studied medications will be evaluated by means of clinical adverse events, physical examination and laboratory results. The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry.
|Liver Cirrhosis Hepatitis C Virus HIV Infection||Drug: Pegylated interferon alfa-2a and Ribavirin||Phase 2 Phase 3|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Efficacy of High Doses of Both Pegylated Interferon Alfa-2a and Ribavirin for Retreatment of HIV-coinfected Patients With Liver Cirrhosis Due to HCV Genotype 1 or 4 Nonresponders to Previous Standard Therapy.|
- Sustained viral response (undetectable serum HCV-RNA) [ Time Frame: Throughout treatment and 24 weeks after finishing it ]
- Relationships between the plasma interferon an ribavirin concentrations and efficacy [ Time Frame: Throughout treatment and 24 weeks after finishing it. ]
- safety and tolerability of the studied medications [ Time Frame: Throughout treatment and 24 weeks after finishing it ]
- The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry [ Time Frame: baseline and after finishing treatment ]
|Study Start Date:||October 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: PegIFN alfa-2a and Ribavirin
HIV-coinfected patients with compensated cirrhosis by hepatitis C virus, genotype 1 or 4.
Drug: Pegylated interferon alfa-2a and Ribavirin
Pegylated interferon alfa-2a (360 ug per week) plus oral Ribavirin (800 mg b.i.d.) for 48 or 72 weeks. The treatment will be discontinued for patients who did not achieve a reduction with respect to baseline of at least 0.5 log10 IU/ml in plasma RNA-HCV levels at week 4 or 2 log10 UI/ml at week 12 and will be considered as viral failures.
Duration: 48 weeks for patients reaching an undetectable plasma RNA_HCV at week12 and 72 weeks for those without a negative viremia at week 12 but a reduction of at least 2 log10 IU/ml in RNA-HCV levels.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01006031
|Hospital Universitario Reina Sofía|
|Hospitales Universitarios Virgen del Rocío|
|Hospital Universitario de Valme|
|Hospital Universitario Virgen Macarena|
|Study Director:||Luis F Lopez-Cortes, MD, PhD||Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocío|
|Principal Investigator:||Luis F Lopez-Cortes, MD, PhD||Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocio|
|Principal Investigator:||Antonio Rivero, MD, PhD||Hospital Universitario Reina Sofia. Cordoba|
|Principal Investigator:||Mª Jose Rios-Villegas, MD, PhD||Hospital Universitario Viren MAcarena. Sevilla|
|Principal Investigator:||Juan A. Pineda, MD, PhD||Hospital Universitario de Valme. Sevilla|