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Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy

21 de fevereiro de 2018 atualizado por: AIDS Clinical Trials Group

A Pilot Study of Lopinavir/Ritonavir in Participants Experiencing Virologic Relapse on NNRTI-Containing Regimens

Most anti-HIV regimens include a non-nucleoside reverse transcriptase inhibitor (NNRTI); however, some individuals fail on these regimens. The purpose of this study is to evaluate the safety and effectiveness of the protease inhibitor (PI) lopinavir/ritonavir (LPV/r) in HIV infected individuals who are failing an anti-HIV regimen that includes an NNRTI.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

Standard effective antiretroviral therapy for HIV infected individuals includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a PI or an NNRTI. However, three-drug regimens may not be ideal in resource-limited settings, where viral load and resistance testing may not be readily available. The purpose of this study is to evaluate the safety and efficacy of the PI LPV/r alone in treatment-experienced, PI-naive HIV infected individuals who are experiencing virologic failure on three-drug regimens.

This study will last 104 weeks. All participants will receive LPV/r twice daily for up to 104 weeks. Participants who experience virologic failure will receive emtricitabine/tenofovir disoproxil fumarate once daily in addition to LPV/r twice daily for the remainder of the study.

There will be 16 study visits for participants on LPV/r monotherapy and 12 study visits for participants who have intensified LPV/r with emtricitabine/tenofovir disoproxil fumarate. Blood collection and clinical assessment will occur at all visits; urine collection and resistance testing will occur at selected visits.

Tipo de estudo

Intervencional

Inscrição (Real)

123

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Malauí
      • Lilongwe, Malauí
        • University of North Carolina Lilongwe CRS (12001)
  • Tailândia
      • Chiang Mai, Tailândia, 50202
        • Chiang Mai University ACTG CRS (11501)
  • Tanzânia
      • Moshi, Tanzânia
        • Kilimanjaro Christian Medical CRS
  • África do Sul
    • Gauteng
      • Johannesburg, Gauteng, África do Sul
        • Wits HIV CRS (11101)
  • Índia
      • Chennai, Índia
        • Y.R.G Ctr, for AIDS Research and Education (11701)

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria for Step 1 Participants:

  • HIV infected
  • Continuous treatment with a three-drug, NNRTI-containing regimen for at least 6 months prior to study entry
  • Viral load of 1,000 copies/ml or greater and less or equal to 200,000 copies/ml obtained within 30 days of study entry
  • Negative pregnancy test within 48 hours of study entry
  • Willing to use acceptable forms of contraception for the duration of the study

  • Laboratory values obtained within 30 days of study entry:

    • Hemoglobin greater or equal to 8.0 g/dL
    • Platelet count greater or equal to 50,000/mm3
    • Estimated Creatinine Clearance greater or equal to 60 mL/min x ULN
    • AST (SGOT), ALT (SGPT) and alkaline phosphatase < 3 x ULN
    • Total bilirubin less or equal to 2.5 x ULN
  • Ability and willingness of participant or legal guardian/representative to give informed consent

Inclusion Criteria for Step 2 Participants:

  • Virologic failure on LPV/r monotherapy defined as viral load of 400 copies/ml or greater after 24 consecutive weeks on LPV/r monotherapy OR virologic failure after initial viral suppression on LPV/r monotherapy
  • Estimated creatinine clearance of 60 ml/min or greater
  • Negative pregnancy test within 48 hours of entry into Step 2
  • Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria for All Participants:

  • Breastfeeding
  • Known allergy or sensitivity to study drugs
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study adherence to study requirements
  • History of chronic hepatitis B infection

Exclusion Criteria for Step I Participants:

  • Prior use of any protease inhibitor treatment
  • Acute therapy for any serious medical condition within 14 days of study entry. For ongoing or chronic therapy, the participant must be on the treatment regimen for at least 14 days, and clinically stable prior to entry. If a potential participant has TB and has received treatment for more than 2 weeks, the TB treatment would have to be modified to include a rifabutin-containing regimen. TB compatible syndromes will also be carefully evaluated prior to entry.

Exclusion Criteria for Step 2 Participants:

- Active opportunistic infection, including tuberculosis (TB)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: LPV/r monotherapy
Participants will receive lopinavir/ritonavir twice daily for up to 104 weeks. Upon confirmation of virologic failure, emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) once a day will be added to their regimen.
Medicamento: Emtricitabine/Tenofovir disoproxil fumarate
Once daily
Outros nomes:
  • Truvada
Medicamento: Lopinavir/Ritonavir
Twice daily
Outros nomes:
  • Kaletra, Aluvia

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy
Prazo: From study entry to week 24
Virologic success at week 24 on LPV/r monotherapy was defined as remaining on LPV/r monotherapy at week 24 without prior virologic failure. Virologic failure was met with either of these two conditions: (i) failure to suppress HIV-1 RNA to < 400 copies/mL by week 24 or (ii) confirmed HIV-1 RNA >= 400 copies/mL after confirmed HIV-1 RNA < 400 copies/mL.
From study entry to week 24
Probability of Grade 3 or 4 Sign or Symptom, or Laboratory Toxicity Over 24 Weeks on Study.
Prazo: From study entry to week 24
Probability of Grade 3 or 4 sign or symptom, or laboratory toxicity over 24 weeks on study using Kaplan-Meier estimates of the cumulative probability of Grade 3 or 4 sign or symptom, or laboratory toxicity at week 24. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
From study entry to week 24

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.
Prazo: Screening
Number of screened subjects with at least one NNRTI, or NRTI-associated resistance mutation. Resistance interpretations used the November 30, 2011 Stanford algorithm.
Screening
Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure.
Prazo: Study entry to Week 104
25th percentile in weeks from study entry to treatment failure, defined as the first occurrence of death, disease progression, or virologic failure. Virologic failure was defined as HIV-1 >= 400 copies/mL after week 24 or 2 consecutive HIV-1 RNA >= 400 copies/mL after week 16 following suppression on LPV/r monotherapy.
Study entry to Week 104
Number of Participants With Study-targeted Diagnoses and Clinical Events
Prazo: Study entry to week 104
Cardiac disorders, Infections and infestations, Metabolism and nutrition disorders, Neoplasms benign, malignant and unspecified (including cysts and polyps), Pregnancy, puerperium and perinatal conditions, Vascular disorders, were specified a priori as study-targeted events by the study chair.
Study entry to week 104
Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure.
Prazo: At time of virologic failure
Number of subjects with at least one new PI-associated resistance mutation at time of virologic failure. Resistance interpretations used the May 6, 2009 Stanford algorithm.
At time of virologic failure
Percentage of Subjects Reporting Not Skipping Medications in the Last Month.
Prazo: Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
The percentage of subjects reporting never missing medications in the last month.
Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
Time to First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification
Prazo: From LPV/r intensification to week 104
25th percentile in weeks from study entry to first new grade 3 or 4 sign or symptom or laboratory toxicity following LPV/r intensification. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
From LPV/r intensification to week 104
Level of HIV-1 RNA as Ascertained From Paired DBS and Plasma
Prazo: At study entry and weeks 24 and 48
Proportion of DBS samples with HIV-1 RNA level <= 400 copies/mL, proportion of plasma samples with HIV-1 RNA level <= 400 copies/mL and proportion of paired DBS and plasma samples that are concordant (both <= 400 copies/mL or both > 400 copies/mL). Results are pooled over 4 different storage temperature conditions (-80C, -20C, 4C and room temperature).
At study entry and weeks 24 and 48
HIV-1 Viral Sequence as Ascertained From Paired DBS and Plasma
Prazo: At study entry and virologic failure
HIV-1 viral sequencing as ascertained from paired DBS and plasma
At study entry and virologic failure
Proportion of Participants With Plasma HIV-1 RNA Levels < 400 Copies/mL From Baseline to Week 104
Prazo: At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
Change in CD4+ Cell Counts From Study Entry to Week 104
Prazo: Study entry and week 104
Study entry and week 104

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

AIDS Clinical Trials Group

Colaboradores

National Institute of Allergy and Infectious Diseases (NIAID)

Investigadores

  • Cadeira de estudo: Nagalingeswaran Kumarasamy, MBBS, PhD, Y. R. Gaitonde Centre for AIDS Research and Education
  • Cadeira de estudo: John Bartlett, MD, Division of Infectious Diseases, Duke University Medical Center

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de janeiro de 2008

Conclusão Primária (Real)

1 de outubro de 2010

Conclusão do estudo (Real)

1 de maio de 2012

Datas de inscrição no estudo

Enviado pela primeira vez

25 de julho de 2006

Enviado pela primeira vez que atendeu aos critérios de CQ

25 de julho de 2006

Primeira postagem (Estimativa)

27 de julho de 2006

Atualizações de registro de estudo

Última Atualização Postada (Real)

20 de março de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

21 de fevereiro de 2018

Última verificação

1 de fevereiro de 2018

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • ACTG A5230
  • 1U01AI068636 (Concessão/Contrato do NIH dos EUA)

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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