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

21. februar 2018 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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

Intervensjonell

Registrering (Faktiske)

123

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Legemiddel: Emtricitabine/Tenofovir disoproxil fumarate
Once daily
Andre navn:
  • Truvada
Legemiddel: Lopinavir/Ritonavir
Twice daily
Andre navn:
  • Kaletra, Aluvia

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy
Tidsramme: 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.
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Study entry and week 104
Study entry and week 104

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

AIDS Clinical Trials Group

Samarbeidspartnere

National Institute of Allergy and Infectious Diseases (NIAID)

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. januar 2008

Primær fullføring (Faktiske)

1. oktober 2010

Studiet fullført (Faktiske)

1. mai 2012

Datoer for studieregistrering

Først innsendt

25. juli 2006

Først innsendt som oppfylte QC-kriteriene

25. juli 2006

Først lagt ut (Anslag)

27. juli 2006

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

20. mars 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. februar 2018

Sist bekreftet

1. februar 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ACTG A5230
  • 1U01AI068636 (U.S. NIH-stipend/kontrakt)

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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