Efficacy of PTX+IFN Alpha+ RBV on Hepatitis C Virus Coinfected HIV Patients
Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860
Current Hepatitis C virus (HCV) treatment consists of the combination of interferon alpha 2a (IFN-alpha 2a) plus ribavirin (RBV) and it provides sustained virologic responses (SVR) on 54 to 56% on HCV monoinfected patients and this response is even lower on HIV-HCV coinfected patients. A previous study on HCV monoinfected patients showed that the addition of pentoxyfylline (PTX) to a treatment scheme based on interferon-alfa and ribavirin increased SVR on 25%, although it is not known if the same effect is to be obtained in HCV-HIV coinfected patients.
On the other hand, other factors such as host genetics, have proved to influence treatment response on HCV infected patients. The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes.
Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860.
HIV-HCV coinfected subjects currently receiving Highly active antiretroviral therapy (HAART), with at least 8 months on undetectable HIV viral load and T helper cells count of 200 or higher will be included. Patients will be randomized on one of two groups:
- Group A: IFN alpha 2a + RBV + PTX
- Group B: IFN alpha 2a + RBV + placebo
Patients will be followed for primary outcome during 72 (for rapid responders) or 96 weeks (for non rapid responses). Outcome measures will be the following:
- SVR rate 24 weeks after the end of treatment
- Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index)
- IL28B rs12979860 genotype
The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Jalisco
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Guadalajara, Jalisco, México, 44280
- Hospital Civil de Guadalajara
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- HIV/HCV coinfected patients
- 18 to 65 years old
- currently receiving HAART
- non-pregnant women
- HIV infection controlled as: undetectable viral load (<40 copies/mL) for at least 8 months and T helper cells count of 200 cells/μL or above
- no contraindications to IFN alpha2a, RBV or PTX treatment
- sign informed consent form
- laboratory parameters within acceptable ranges
Exclusion Criteria:
- Women that present a positive pregnancy test during the study
- Patients that for any reason no longer wish to receive IFN alpha2a, RBV or PTX treatment
- Serious adverse events that prevent to continue IFN alpha2a, RBV or PTX treatment; such as severe neutropenia, severe thrombocytopenia or severe anemia
- Presence of an opportunistic infection or malignancy that requires treatment with drugs interacting with IFN alpha2a, RBV or PTX
- Patients that fail to adhere to treatment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: PTX
IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral PTX 400 mg each 12 h, oral
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Addition of pentoxifylline to current HCV treatment
|
|
Comparador de placebos: Placebo
IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral Placebo oral daily
|
Placebo matching pentoxifylline dosage
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection
Periodo de tiempo: SVR rate at 24 weeks after the end of therapy
|
Primary objective: is to evaluate sustained virologic response at post treatment week 24 following treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection
|
SVR rate at 24 weeks after the end of therapy
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
grade of hepatic fibrosis
Periodo de tiempo: Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)
|
The liver stiffness (hepatic fibrosis) will be measured by transient elastography and the APRI index on the baseline visit and then at the follow up visit after treatment, which will be after 72 weeks, for patients that turn out to be quick responders; or 96 weeks, for patients that turn out to be non-quick responders.
|
Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)
|
|
rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates
Periodo de tiempo: RVR at week 4 and eRVR at week 48 post treatment
|
secondary objective (2): Evaluate rapid virologic response (RVR) and extended rapid virologic response (eRVR)
|
RVR at week 4 and eRVR at week 48 post treatment
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism
Periodo de tiempo: week 72
|
We will compare the percentage of patients with CC genotype among patients that achieved sustained virologic response and those who did not achieved it.
This is to confirm if the intervention provides a beneficial effect, irrespectively of host genetic factors.
|
week 72
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Infecciones por virus de ARN
- Enfermedades virales
- Infecciones
- Infecciones transmitidas por la sangre
- Enfermedades contagiosas
- Enfermedades del HIGADO
- Infecciones por Flaviviridae
- Hepatitis, Viral, Humana
- Hepatitis
- Hepatitis C
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes vasodilatadores
- Inhibidores de enzimas
- Inhibidores de la agregación plaquetaria
- Agentes Protectores
- Antioxidantes
- Inhibidores de la fosfodiesterasa
- Eliminadores de radicales libres
- Agentes de protección contra la radiación
- Pentoxifilina
Otros números de identificación del estudio
- PTX-HCV/HIV
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