Clinical trial NCT01006031: Retreatment With High Doses of pegIFN Alfa-2a and Ribavirin of Previous Nonresponders HIV-coinfected Patients With Cirrhosis Due to HCV 1-4
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Liver Cirrhosis
Hepatitis C Virus
HIV Infection
Keywords: Liver cirrhosis
Hepatitis C virus
HIV infection
Pegylated interferon alfa-2a
Ribavirin
Treatment experienced
Lead sponsor: Sociedad Andaluza de Enfermedades Infecciosas
Sponsor class: NETWORK
First posted: 2009-11-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Sustained viral response (undetectable serum HCV-RNA)
timeFrame: Throughout treatment and 24 weeks after finishing it
Secondary outcomes:
measure: Relationships between the plasma interferon an ribavirin concentrations and efficacy
timeFrame: Throughout treatment and 24 weeks after finishing it.
measure: safety and tolerability of the studied medications
timeFrame: Throughout treatment and 24 weeks after finishing it
measure: The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry
timeFrame: baseline and after finishing treatment
Other outcomes:
Locations:
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Seviila
country: Spain
facility: Hospitales Universitarios Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocío
name: Luis F Lopez-Cortes, MD, PhD
role: STUDY_DIRECTOR
affiliation: Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocio
name: Luis F Lopez-Cortes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Reina Sofia. Cordoba
name: Antonio Rivero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Viren MAcarena. Sevilla
name: Mª Jose Rios-Villegas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Valme. Sevilla
name: Juan A. Pineda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: