Retreatment With High Doses of pegIFN Alfa-2a and Ribavirin of Previous Nonresponders HIV-coinfected Patients With Cirrhosis Due to HCV 1-4

NCT ID: NCT01006031

Last Updated: 2011-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-12-31

Brief Summary

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.

Conditions

Liver Cirrhosis; Hepatitis C Virus; HIV Infection

Keywords

Liver cirrhosis; Hepatitis C virus; HIV infection; Pegylated interferon alfa-2a; Ribavirin; Treatment experienced

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PegIFN alfa-2a and Ribavirin

HIV-coinfected patients with compensated cirrhosis by hepatitis C virus, genotype 1 or 4.

Group Type: EXPERIMENTAL

Pegylated interferon alfa-2a and Ribavirin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Pegasys; Copegus

Eligibility Criteria

Inclusion Criteria

• Age older than 18 years
• 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.
• Women of child-bearing age: negative pregnancy test
• Ability to understand and sign a written consent form

Exclusion Criteria

• HCV genotypes different to 1 or 4
• Acute or chronic hepatitis B infection (positivity for hepatitis B surface antigen or plasma DNA) or other concomitant causes of liver disease
• Pregnancy or breast feeding.
• Decompensated liver disease at baseline.
• Neutropenia <1000/uL, anemia <100 g/L or thrombocytopenia <20.000/uL.
• Creatinine clearance < 50 mL/min.
• Concomitant treatment with immunomodulators or zidovudine, didanosine or stavudine.
• Organ or bone marrow transplantation
• Current alcoholism or iv drug abuse. Methadone is allowed.
• Current neoplasm and/or anti-tumor chemotherapy or immunomodulators
• Psychosis or uncontrolled clinical depression
• Auto-immune disease, including auto-immune hepatitis
• History of significant cardiovascular disease (NYHA III-IV) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure.
• Thyroid dysfunction.
• Clinically significant retinal abnormalities
• Inability to understand and sign a written consent form

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sociedad Andaluza de Enfermedades Infecciosas

NETWORK

Sponsor Role: lead

Responsible Party

Antonio Rivero

Luis Fernando Lopez-Cortes

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luis F Lopez-Cortes, MD, PhD

Role: STUDY_DIRECTOR

Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocío

Luis F Lopez-Cortes, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocio

Antonio Rivero, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Reina Sofia. Cordoba

Mª Jose Rios-Villegas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Viren MAcarena. Sevilla

Juan A. Pineda, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de Valme. Sevilla

Locations

Hospital Universitario Reina Sofía

Córdoba, , Spain

Hospitales Universitarios Virgen del Rocío

Seviila, , Spain

Hospital Universitario de Valme

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

Spain

Other Identifiers

HEPAVIR_IFN_2009

Identifier Type: -

Identifier Source: org_study_id