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Steady State PK in Malnourished HIV Infected Children (P1092)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01818258
First received: January 14, 2013
Last updated: June 26, 2014
Last verified: June 2014

January 14, 2013
June 26, 2014
September 2014
June 2015   (final data collection date for primary outcome measure)
  • Safety/ tolerability of ZDV, 3TC and Lopinavir/ritonavir (LPV/r) in severely and normal/mild malnourished children [ Time Frame: 1, 12 and 24 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    numbers (percent) of subjects with at least Grade 3 adverse events related to study drugs and at least Grade 3 adverse events regardless of the relationship to study drugs.
  • PK exposure comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 24 weeks after initiation of HAART ] [ Designated as safety issue: Yes ]
    Steady-state Area under the curve (AUC) and plasma clearance (CL/F) for ZDV, 3TC, and LPV/r
Same as current
Complete list of historical versions of study NCT01818258 on ClinicalTrials.gov Archive Site
  • Minimum concentration comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 4, 8, 12, 16, 24, 36 and 48 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    To compare the minimum trough concentration of LPV/r between severely malnourished children and children with normal nutrition - mild malnutrition at 1, 4, 8, 12, 16, 24, 36 and 48 weeks following initiation of HAART
  • LPV protein binding comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 12 and 24 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    To investigate the impact of malnutrition on LPV protein binding by comparing the free fraction of LPV in severely malnourished children and children with normal nutrition - mild malnutrition at 1, 12 and 24 weeks.
Same as current
Not Provided
Not Provided
 
Steady State PK in Malnourished HIV Infected Children
Phase IV Evaluation Of The Steady State Pharmacokinetics Of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in Severely Malnourished HIV-1-Infected, Antiretroviral-Naïve Children Who Are Initiating HAART

HIV-infected children from sub-Saharan Africa often present with severe malnutrition as their AIDS defining illness. Severe malnutrition that is not responding to nutritional rehabilitation is an indication to initiate highly active antiretroviral therapy (HAART). In severe malnutrition metabolic and or gut structural derangement may lead to inadequate antiretroviral (ARV) absorption and or erratic drug levels. The greater surface area to weight ratio in severely malnourished children could also place them at higher risk of under dosing compared to children with mild to moderate malnutrition. The paucity of ARV pharmacokinetic (PK) data in these vulnerable severely malnourished children speaks to the need to determine the PKs of ARVs and the most appropriate time to initiate HAART in this group of children. This study will utilize the recommended weight band dosing which simplifies dosing in resource limited settings and is the approach used in the WHO pediatric ARV dosing guidelines. It will also use pediatric formulations which have not been studied before in severely malnourished children. The findings of this study will determine the PK of HAART in this population with the overall goal of determining whether the current recommended doses are optimum doses for severely malnourished children and the most appropriate time to initiate HAART in the severely malnourished child.

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Positive
  • Malnourished
Drug: ZDV+3TC+LPV/r
Zidovudine (ZDV, Retrovir®) will be in a glycerin/sucrose base at a concentration of 10 mg/ml, two times daily orally at the WHO weight band dose for 48 weeks Lamivudine oral solution (Epivir®, 3TC) is for oral administration. One milliliter (1 mL) of lamivudine oral solution contains 10 mg of lamivudine (10 mg/mL), two times daily orally at the WHO weight band dose for 48 weeks Lopinavir 80 mg/ritonavir 20 mg per milliliter oral solution (Kaletra®, LPV/r) contains 42.4% alcohol by volume, two times daily orally at the WHO weight band dose for 48 weeks
  • Active Comparator: Severe Malnutrition

    Both arms got the ZDV+3TC+LPV/r combination drugs. Zidovudine (ZDV, Retrovir®) will be in a glycerin/sucrose base at a concentration of 10 mg/ml, administered two times daily orally at the WHO weight band dose for 48 weeks.

    Lamivudine oral solution (Epivir®, 3TC) is for oral administration. One milliliter (1 mL) of lamivudine oral solution contains 10 mg of lamivudine (10 mg/mL), administered two times daily orally at the WHO weight band dose for 48 weeks.

    Lopinavir 80 mg/ritonavir 20 mg per milliliter oral solution (Kaletra®, LPV/r) contains 42.4% alcohol by volume, administered two times daily orally at the WHO weight band dose for 48 weeks

    Intervention: Drug: ZDV+3TC+LPV/r
  • Active Comparator: Normal Nutrition/Mild Malnutrition

    Both arms got the ZDV+3TC+LPV/r combination drugs. Zidovudine (ZDV, Retrovir®) will be in a glycerin/sucrose base at a concentration of 10 mg/ml, administered two times daily orally at the WHO weight band dose for 48 weeks.

    Lamivudine oral solution (Epivir®, 3TC) is for oral administration. One milliliter (1 mL) of lamivudine oral solution contains 10 mg of lamivudine (10 mg/mL), administered two times daily orally at the WHO weight band dose for 48 weeks.

    Lopinavir 80 mg/ritonavir 20 mg per milliliter oral solution (Kaletra®, LPV/r) contains 42.4% alcohol by volume, administered two times daily orally at the WHO weight band dose for 48 weeks.

    Intervention: Drug: ZDV+3TC+LPV/r
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
50
September 2016
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age >6 to <36 months at entry
  2. Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma.

    Acceptable tests when subjects are ≤18 months of age the first test may be any of the following:

    • One HIV DNA Polymerase Chain Reaction (PCR)
    • One HIV RNA (quantitative >5,000 copies/mL or qualitative)
    • One HIV culture (prior to August 2009)
    • One total HIV nucleic acid If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and NIH approved.

    Acceptable tests when subjects are > 18 months of age

    The first test may be any of the following:

    • Two rapid antibody tests from different manufacturers or based on different principles and epitopes
    • One rapid antibody test AND one [enzyme immunoassay (EIA) OR Western blot (WB) OR immunofluorescence OR chemiluminescence]
    • One EIA AND one [WB OR immunofluorescence OR chemiluminescence]
    • One HIV DNA PCR
    • One HIV RNA (quantitative >5,000 copies/mL or qualitative)
    • One HIV culture (prior to August 2009)
    • One total HIV nucleic acid

    If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) a laboratory participating in an appropriate external quality assurance program and either College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) approved (for US laboratories) or NIH-approved (for international laboratories).

  3. WHO classification for severe malnutrition (non-edematous) and normal nutrition status and mild malnutrition as described below:

    • Severe malnutrition defined as weight for height z (WHZ) score ≤-3 Standard Deviations.
    • Normal nutrition status defined as weight for height z (WHZ) score >-1 Standard Deviations.
    • Mild malnutrition defined as weight for height z (WHZ) score >-2 Standard Deviations ≤-1 Standard Deviations.
  4. Antiretroviral naïve except for ARVs used for prevention of mother-to-child transmission of HIV.
  5. Children with acute serious infection must have been stabilized by at least five days on antimicrobials.
  6. Eligible for HAART as defined by WHO pediatric guidelines described below for infants and children:

    • Initiate ART for all HIV-infected children below 24 months of age irrespective of cluster of differentiation 4 (CD4)count or WHO clinical stage.
    • Initiate ART for all HIV-infected children between 24 and 59 months of age with CD4 count ≤750 cells/mm3 or % CD4 ≤ 25%, whichever is lower, irrespective of WHO clinical stage.
    • Initiate ART for all HIV-infected children with WHO HIV clinical stages 3 and 4, irrespective of CD4 count.
  7. Parent or legal guardian able and willing to provide signed informed consent, remain within the study area during the study period and agree to have subject followed at the clinical site
  8. For severely malnourished children: Clinical improvement after 10 -18 days on nutrition rehabilitation defined as: Appetite returned and eating better - child shows interest in food even if does not complete amount given:

    • Weight gain of about 3-5gm/kg body weight/day for 1-2 days
    • Normalized electrolytes (sodium and potassium)
    • No evidence of cardiac failure
    • Loss of apathy and starting to play
    • Temperature stable - no hypothermia or pyrexia

    For children with normal - mild malnutrition, clinical stability will be indicated by:

    • Good appetite
    • Normalized electrolytes (sodium and potassium)
    • Temperature stable - no hypothermia (<35°C) or pyrexia (>37.8° C)
  9. An inpatient in the nutrition rehabilitation unit

Exclusion Criteria:

  1. Children with edematous malnutrition at the time of study entry
  2. The following laboratory values within 30 days prior to entry:

    • Any ≥ Grade 2 toxicity (except hemoglobin)
    • Hemoglobin <7.5g/dL
  3. ≥ Grade 3 respiratory distress or presence of cardio respiratory compromise
  4. Chemotherapy for active malignancy
  5. Children with an acute Opportunistic Infection (OI) and on appropriate treatment for <5 days
  6. Active tuberculosis disease
  7. Evidence of hepatitis demonstrated by either positive hepatitis B surface antigen or clinical hepatitis as evidenced by jaundice and hepatomegaly
  8. Taking any disallowed medications
  9. Any condition, situation, or clinical finding that in the opinion of the investigator would place the child at an unacceptable level of risk for injury, or render the child/caregiver(s) unable to meet the requirements of the study, interfere with study participation, or in the interpretation of study results.
Both
6 Months to 36 Months
No
Contact: Anne Coletti, MPH 919-544-7040 ext 11238 acoletti@fhi360.org
Tanzania,   Uganda,   Zimbabwe
 
NCT01818258
IMPAACT P1092, U01AI068632
Yes
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Maxensia O Owor, MBChB, MMED International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP