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

HIV Infection Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01006031
• Other study ID #: HEPAVIR_IFN_2009
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 29, 2009
• Last updated: December 28, 2011
• Start date: October 2009
• Est. completion date: December 2011

Study information

• Verified date: December 2011
• Source: Sociedad Andaluza de Enfermedades Infecciosas
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C
• Hepatitis C Virus
• HIV Infection
• HIV Infections
• Liver Cirrhosis

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Cordoba
Spain	Hospitales Universitarios Virgen del Rocío	Seviila
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Sociedad Andaluza de Enfermedades Infecciosas

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained viral response (undetectable serum HCV-RNA)		Throughout treatment and 24 weeks after finishing it	Yes
Secondary	Relationships between the plasma interferon an ribavirin concentrations and efficacy		Throughout treatment and 24 weeks after finishing it.	No
Secondary	safety and tolerability of the studied medications		Throughout treatment and 24 weeks after finishing it	Yes
Secondary	The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry		baseline and after finishing treatment	No