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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Antonio Rivero, Sociedad Andaluza de Enfermedades Infecciosas
ClinicalTrials.gov Identifier:
NCT01006031
First received: October 29, 2009
Last updated: December 28, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Hepatitis C Virus
HIV Infection
Drug: Pegylated interferon alfa-2a and Ribavirin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Sociedad Andaluza de Enfermedades Infecciosas:

Primary Outcome Measures:
  • Sustained viral response (undetectable serum HCV-RNA) [ Time Frame: Throughout treatment and 24 weeks after finishing it ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Relationships between the plasma interferon an ribavirin concentrations and efficacy [ Time Frame: Throughout treatment and 24 weeks after finishing it. ] [ Designated as safety issue: No ]
  • safety and tolerability of the studied medications [ Time Frame: Throughout treatment and 24 weeks after finishing it ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: October 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Other Names:
  • Pegasys
  • Copegus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006031

Locations
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, Spain
Sponsors and Collaborators
Sociedad Andaluza de Enfermedades Infecciosas
Investigators
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
  More Information

No publications provided

Responsible Party: Antonio Rivero, Luis Fernando Lopez-Cortes, Sociedad Andaluza de Enfermedades Infecciosas
ClinicalTrials.gov Identifier: NCT01006031     History of Changes
Other Study ID Numbers: HEPAVIR_IFN_2009
Study First Received: October 29, 2009
Last Updated: December 28, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Sociedad Andaluza de Enfermedades Infecciosas:
Liver cirrhosis
Hepatitis C virus
HIV infection
Pegylated interferon alfa-2a
Ribavirin
Treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis C
Infection
Liver Cirrhosis
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014