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

Sponsor:	Sociedad Andaluza de Enfermedades Infecciosas
Information provided by:	Sociedad Andaluza de Enfermedades Infecciosas
ClinicalTrials.gov Identifier:	NCT01006031

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 II Phase III

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS Cirrhosis Hepatitis Hepatitis C

Drug Information available for: Ribavirin Interferon alfa-2a Peginterferon Alfa-2a Interferon alfa-n1 Interferons

U.S. FDA Resources

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 ]

Estimated Enrollment:	30
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
PegIFN alfa-2a and Ribavirin: Experimental 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.

Arms

Assigned Interventions

PegIFN alfa-2a and Ribavirin: Experimental

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.

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

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

Contacts

Contact: Luis F Lopez-Cortes, PhD

34-955013096

lflopez@telefonica.net

Locations

Spain
Hospitales Universitarios Virgen del Rocío	Recruiting
Seviila, Spain
Contact: Luis F Lopez-Cortes, MD, PhD 34-955013094 lflopez@telefonica.net
Principal Investigator: Luis F Lopez-Cortes, MD, PhD
Hospital Universitario Reina Sofía	Recruiting
Cordoba, Spain
Contact: Antonio Rivero, MD, PhD ariveror@gmail.com
Principal Investigator: Antonio Rivero, md, pHd
Hospital Universitario Virgen Macarena	Recruiting
Sevilla, Spain
Contact: Mª Jose Rios-Villegas, MD, PhD mjriosvillegas@terra.es
Principal Investigator: Mª Jose Rios-Villegas, MD, PhD
Hospital Universitario de Valme	Recruiting
Sevilla, Spain
Contact: Juan A Pineda, MD, PhD japineda@telefonica.net
Principal Investigator: Juan A Pineda, MD, PhD

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:	Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocio ( Luis Fernando Lopez-Cortes )
Study ID Numbers:	HEPAVIR_IFN_2009
Study First Received:	October 29, 2009
Last Updated:	November 6, 2009
ClinicalTrials.gov Identifier:	NCT01006031 History of Changes
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:

Antimetabolites
Anti-Infective Agents
Communicable Diseases
Sexually Transmitted Diseases, Viral
Liver Diseases
Interferon Type I, Recombinant
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Flaviviridae Infections
Antineoplastic Agents
Fibrosis
Physiological Effects of Drugs
Ribavirin
Hepatitis, Viral, Human

Liver Cirrhosis
Infection
Pathologic Processes
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Hepatitis C
Retroviridae Infections
Interferon-alpha
RNA Virus Infections
Immune System Diseases
Growth Substances
Interferons
Acquired Immunodeficiency Syndrome
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on November 30, 2009