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

21 februari 2018 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

123

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Indië
      • Chennai, Indië
        • Y.R.G Ctr, for AIDS Research and Education (11701)
  • Malawi
      • Lilongwe, Malawi
        • University of North Carolina Lilongwe CRS (12001)
  • Tanzania
      • Moshi, Tanzania
        • Kilimanjaro Christian Medical CRS
  • Thailand
      • Chiang Mai, Thailand, 50202
        • Chiang Mai University ACTG CRS (11501)
  • Zuid-Afrika
    • Gauteng
      • Johannesburg, Gauteng, Zuid-Afrika
        • Wits HIV CRS (11101)

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: Emtricitabine/Tenofovir disoproxil fumarate
Once daily
Andere namen:
  • Truvada
Geneesmiddel: Lopinavir/Ritonavir
Twice daily
Andere namen:
  • Kaletra, Aluvia

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy
Tijdsspanne: 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.
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.
Tijdsspanne: 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.
Tijdsspanne: 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
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Study entry and week 104
Study entry and week 104

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

AIDS Clinical Trials Group

Medewerkers

National Institute of Allergy and Infectious Diseases (NIAID)

Onderzoekers

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

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 januari 2008

Primaire voltooiing (Werkelijk)

1 oktober 2010

Studie voltooiing (Werkelijk)

1 mei 2012

Studieregistratiedata

Eerst ingediend

25 juli 2006

Eerst ingediend dat voldeed aan de QC-criteria

25 juli 2006

Eerst geplaatst (Schatting)

27 juli 2006

Updates van studierecords

Laatste update geplaatst (Werkelijk)

20 maart 2018

Laatste update ingediend die voldeed aan QC-criteria

21 februari 2018

Laatst geverifieerd

1 februari 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ACTG A5230
  • 1U01AI068636 (Subsidie/contract van de Amerikaanse NIH)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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