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Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia

11 de noviembre de 2019 actualizado por: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia

CCR5 antagonists might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity. The assessment of HIV-1 tropism in proviral DNA could be helpful to inform in which of these subjects CCR5 antagonists could be efficacious.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

The assessment of HIV-1 tropism is needed before starting treatment with a CCR5-antagonist. Several phenotypic and genotyping tropism tests have been developed in the recent years. Phenotypic assays (i.e. TrofileTM and ES-TrofileTM) have been used.in most clinical trials. Genotypic tropism testing, however, is easier, cheaper and faster than phenotypic methods, and can be performed in a local HIV laboratories.

Viral RNA amplification is difficult in subjects with HIV-1 RNA levels <500-1000 copies/mL. In these cases, the optimal source of genetic material is peripheral blood mononuclear cell (PBMC)-associated proviral DNA. Whereas genotypic tropism testing in proviral DNA is technically feasible, it has not been validated as a tool to predict sustained virological response to CCR5-antagonist therapy in subjects with undetectable viremia.

As of today, maraviroc is the only CCR5-antagonist approved for HIV treatment. It has few drug interactions and a good security profile, particularly in terms of lipid and glucose metabolism. Therefore, it might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity or metabolic problems.

This study will evaluate 48-week virological outcomes in aviremic subjects with an R5 virus by proviral genotypic tropism testing who switch the "third drug" of their regimen to maraviroc.

Tipo de estudio

Intervencionista

Inscripción (Actual)

74

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • España
      • Alicante, España, 03010
        • Hospital Gral. U. de Alicante
      • Barcelona, España, 08035
        • Hospital Vall d'Hebron
      • Barcelona, España, 08304
        • Hospital de Mataro
      • Granada, España, 18014
        • Hospital Virgen de las Nieves
      • Granada, España, 28012
        • Hospital U. San Cecilio
      • Madrid, España, 28040
        • Hospital Clinico San Carlos
      • Madrid, España, 28007
        • Hospital U. Gregorio Marañón
      • Madrid, España, 28034
        • Hospital Ramón y Cajal
      • Madrid, España, 28029
        • Hospital Carlos III
      • Murcia, España, 30003
        • Hospital Reina Sofía de Murcia
      • Tarragona, España, 43007
        • Hospital Sant Pau i Santa Tecla
      • Valencia, España, 46015
        • Hospital Arnau de Vilanova
      • Valencia, España, 46009
        • Hospital La Fe
      • Valencia, España, 46014
        • Hospital Gral. U. de Valencia
      • Valencia, España, 46017
        • Hospital U. Dr. Peset
    • A Coruña
      • Santiago de Compostela, A Coruña, España, 15781
        • Hospital Xeral de Vigo
    • Alicante
      • Elche, Alicante, España, 03203
        • Hospital de Elche
    • Baleares
      • Palma de Mallorca, Baleares, España, 07011
        • Hospital Son Espases
    • Barcelona
      • Badalona, Barcelona, España, 08916
        • H. U. Germans Trias i Pujol
      • Hospitalet de Llobregat, Barcelona, España, 08907
        • H. de Bellvitge
    • Cantabria
      • Santander, Cantabria, España, 39011
        • Hospital U. Marques de Valdecilla
    • Castelló
      • Castelló De La Plana, Castelló, España, 12004
        • Hospital General de Castellon
    • Murcia
      • Cartagena, Murcia, España, 30203
        • Hospital Sta. Lucía/ H. Sta. Mª del Rosell
    • Vizcaya
      • Bilbao, Vizcaya, España, 48903
        • Hospital de Cruces

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 99 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. HIV-1 infected patients.
  2. Age 18 or more.
  3. Antiretroviral treatment containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) plus 1 Non-nucleoside reverse-transcriptase inhibitor (NNRTI) or 1 protease inhibitor (PI) or 1 integrase inhibitor (ININ)
  4. Patients receiving stable antiretroviral treatment for at least 6 months.
  5. Viral load under 50 copies/mL in the last 6 months
  6. Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method.
  7. A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria.
  8. An antiretroviral regimen containing a CCR5-antagonist is suitable for the patient (physician criteria).
  9. Voluntary written informed consent.

Exclusion Criteria:

  1. Pregnancy or breast-feeding.
  2. Patient previously treated with maraviroc.
  3. Patients with documented resistance to maraviroc or any other drug considered for the new ARV regimen.
  4. Viral failure in the moment of inclusion.
  5. Bad adherence history or anticipated (investigator criteria).

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Ciencia básica
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Droga: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Percentage of patients with viral load under 50 copies/mL
Periodo de tiempo: Week 48
Week 48

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of patients without confirmed virological failure.
Periodo de tiempo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Time to loss of virological response (TLOVR) < 200 copies/mL
Periodo de tiempo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Time to loss of virological response (TLOVR) < 50 copies/mL
Periodo de tiempo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Periodo de tiempo: Week 12
To evaluate other aspects related to maintanence of virological response
Week 12
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Periodo de tiempo: Week 24
To evaluate other aspects related to maintanence of virological response
Week 24
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Periodo de tiempo: Week 36
To evaluate other aspects related to maintanence of virological response
Week 36
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Periodo de tiempo: Week 48
To evaluate other aspects related to maintanence of virological response.
Week 48
Time to treatment discontinuation, overall, and due to factors other than loss of virological response
Periodo de tiempo: Up to week 48
To evaluate other aspects related to maintanence of virological response
Up to week 48
Association between pre-treatment level of X4 viruses detected by deep sequencing at screening and virological response to maraviroc based therapy at week 48.
Periodo de tiempo: Week 48
To evaluate changes in HIV tropism
Week 48
Level of X4 viruses by detected by population sequencing.
Periodo de tiempo: Screening (up to 48 weeks)
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Screening (up to 48 weeks)
Level of X4 viruses by detected by population sequencing.
Periodo de tiempo: Week 12
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 12
Level of X4 viruses by detected by population sequencing.
Periodo de tiempo: Week 48
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 48
Level of X4 viruses by detected by deep sequencing.
Periodo de tiempo: Screening (up to 48 weeks)
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Screening (up to 48 weeks)
Level of X4 viruses by detected by deep sequencing.
Periodo de tiempo: Week 12
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 12
Level of X4 viruses by detected by deep sequencing.
Periodo de tiempo: Week 48
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 48
High-resolution assessment of virus diversity and X4 level using deep sequencing
Periodo de tiempo: Week 12
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
Week 12
High-resolution assessment of virus diversity and X4 level using deep sequencing
Periodo de tiempo: In case of virological failure (week 12 up to virological failure)
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
In case of virological failure (week 12 up to virological failure)
Median change of total cholesterol.
Periodo de tiempo: From baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From baseline to week 48.
Median change of HDL cholesterol.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of LDL cholesterol.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of triglycerides
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of AST serum levels.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of ALT serum levels.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of alkaline phosphatase serum levels.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of total bilirubin serum levels.
Periodo de tiempo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Cumulative number of adverse events
Periodo de tiempo: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of adverse events
Periodo de tiempo: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of adverse events
Periodo de tiempo: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of adverse events
Periodo de tiempo: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of adverse events
Periodo de tiempo: Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Cumulative number of grade 3-4 adverse events
Periodo de tiempo: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of grade 3-4 adverse events
Periodo de tiempo: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of grade 3-4 adverse events
Periodo de tiempo: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of grade 3-4 adverse events
Periodo de tiempo: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of grade 3-4 adverse events
Periodo de tiempo: Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Proportion of patients withdrawn from the study and reason for study withdrawal
Periodo de tiempo: Up to week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Up to week 48

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de junio de 2011

Finalización primaria (Actual)

1 de abril de 2014

Finalización del estudio (Actual)

1 de mayo de 2014

Fechas de registro del estudio

Enviado por primera vez

17 de junio de 2011

Primero enviado que cumplió con los criterios de control de calidad

22 de junio de 2011

Publicado por primera vez (Estimar)

23 de junio de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

14 de noviembre de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

11 de noviembre de 2019

Última verificación

1 de julio de 2014

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • PROTEST

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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