HIV PositivePhase 4NCT01818258
IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children
A Phase 4 study testing ZDV+3TC+LPV/r in people with HIV Positive and Malnourished, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 5 sites in 4 countries.
Trial summary
Children living with HIV from sub-Saharan Africa often present with severe malnutrition. In severe malnutrition, metabolic and/or gut structural derangement may lead to inadequate antiretroviral (ARV) absorption and/or erratic drug levels. Read more about this study
- Who is it for?
- Ages 6 to 36 months
- Conditions the study is for
- HIV Positive, Malnourished
- What is being tested?
- ZDV+3TC+LPV/r
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 26 Oct 2015to 29 Sep 2017
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Documentation of HIV-1 infection defined as positive results from two samples collected at different time points, using protocol-specified tests
- Meets WHO classification for severe malnutrition, normal nutrition status, or mild malnutrition
- Eligible for HAART defined by WHO 2013 pediatric guidelines
- 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
- Qualifying hematology and chemistry laboratory values obtained from specimens collected within the study-specific screening period
- For severely malnourished children: An inpatient in a nutrition rehabilitation unit. 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:
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- No further weight loss
- Normalized sodium and potassium defined as severity grade 1 or lower
- No evidence of cardiac failure
- Loss of apathy and starting to play
- No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or >34.4 to <37.4° C (axillary)
- For children with normal - mild malnutrition, clinical stability will be indicated by:
- Good appetite
- Normalized sodium and potassium defined as severity grade 1 or lower
- No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or >34.4 to <37.4° C (axillary)
Who cannot join
- Edematous malnutrition at the time of study entry
- ≥ Grade 3 respiratory distress or presence of cardio respiratory compromise within 3 days prior to entry
- Chemotherapy for malignancy
- Acute infection for which the child has received appropriate antimicrobial treatment for <5 days
- Tuberculosis disease
- Clinic hepatitis as evidenced by jaundice and hepatomegaly
- Taking any disallowed medications
- 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.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Uganda1 site
Makerere University-Johns Hopkins University (MUJHU) Research Collaboration (30293)
Kampala
About this study
Official title: IMPAACT 1092: Phase IV Evaluation Of The Steady State Pharmacokinetics Of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in Severely Malnourished HIV-1-Infected Children
Children living with HIV from sub-Saharan Africa often present with severe malnutrition. 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. However, limited data are available on the pharmacokinetics of ARVs in severely malnourished children. This study addressed this critical gap in knowledge by evaluating the PK of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in severely malnourished children living with HIV, compared to children with normal nutrition to mild malnutrition living with HIV.
Read the detailed description
P1092 was a prospective, non-randomized Phase IV open label study of antiretroviral drugs zidovudine (ZDV), lamivudine (3TC), and ritonavir boosted lopinavir (LPV/r) in children living with HIV aged 6 to less than 36 months grouped by nutritional status. The study's primary objectives were to characterize the pharmacokinetics (PK), safety, and tolerability of antiretroviral (ARV) regimens in severely acute malnourished (SAM) children following the initiation of nutritional rehabilitation and compare results to mildly malnourished or normally nourished children in order to determine if current recommended doses are optimal in severely malnourished children.
Two cohorts of children were enrolled based on nutritional status at screening: severely acute malnourished children and children with mild malnutrition or normal nutrition (non-SAM cohort). SAM participants were recruited from nutritional rehabilitation clinics while non-SAM participants were enrolled from HIV treatment centers. SAM participants were required to complete a 10 to 18 day nutritional rehabilitation program before entering the study. A World Health Organization (WHO, 2013) approach to management of SAM was used. All participants were to receive an antiretroviral regimen of ZDV+3TC+LPV/r. ARVs were dosed based on WHO weight band dosing and were to be administered twice per day in a pediatric liquid formulation. ZDV was allowed to be replaced with abacavir at the discretion of the site investigator/clinician in cases of grade 3 or higher hematologic toxicity on a ZDV-inclusive regimen or ZDV intolerance. Participants were followed for 48 weeks.
- Conditions
- HIV Positive, Malnourished
- Being tested
- ZDV+3TC+LPV/r
- Keywords
- HIV, Children, HAART, Malnourished
- Medical subject headings
- HIV Seropositivity, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZDV+3TC+LPV/rDrug
Also called Zidovudine, Retrovir, Lamivudine, Epivir
| Study group | Role | What they receive |
|---|---|---|
| Severe Malnutrition | Active comparator | ZDV+3TC+LPV/r Zidovudine (ZDV, Retrovir®) 10 mg/ml oral syrup administered twice daily at WHO weight band dose for 48 weeks; Lamivudine (Epivir®, 3TC) 10 mg/ml for oral solution administered twice daily at WHO weight band dose for 48 weeks; Lopinavir/ritonavir (Kaletra®, LPV/r) 80/20 mg/ml oral solution administered twice daily at the WHO weight band dose for 48 weeks Receives: Drug: ZDV+3TC+LPV/r |
| Normal Nutrition/Mild Malnutrition | Active comparator | ZDV+3TC+LPV/r Zidovudine (ZDV, Retrovir®) 10 mg/ml oral syrup administered twice daily at WHO weight band dose for 48 weeks; Lamivudine (Epivir®, 3TC) 10 mg/ml for oral solution administered twice daily at WHO weight band dose for 48 weeks; Lopinavir/ritonavir (Kaletra®, LPV/r) 80/20 mg/ml oral solution administered twice daily at the WHO weight band dose for 48 weeks Receives: Drug: ZDV+3TC+LPV/r |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade 3 or Higher Adverse Events Through 24 Weeks
Number (percent) of participants with at least one grade 3 or higher adverse event (AE) regardless of the relationship to study drugs.
Measured: From week 0 to week 24
Grade 3 or Higher Adverse Events Related to Study Drugs Through Week 24
Number (percent) of participants with at least one Grade 3 or higher adverse event related to study drugs
Measured: From week 0 to week 24
Steady-state Lopinavir Area Under the Curve
Steady-state area under the curve (AUC) for Lopinavir (LPV)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Plasma Clearance of Lopinavir
Steady-state plasma clearance (CL/F) of LPV
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Steady-state Ritonavir Area Under the Curve
Steady-state area under the curve (AUC) for Ritonavir (RTV)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Plasma Clearance of Ritonavir
Steady-state plasma clearance (CL/F) of RTV
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Steady-state Lamivudine Area Under the Curve
Steady-state area under the curve (AUC) of Lamivudine (3TC)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Plasma Clearance of Lamivudine
Steady-state plasma clearance (CL/F) of Lamivudine (3TC)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Steady-state Zidovudine Area Under the Curve
Steady-state area under the curve (AUC) of zidovudine (ZDV)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Plasma Clearance of Zidovudine
Steady-state plasma clearance (CL/F) of Zidovudine (ZDV)
Measured: 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 12, and 24 weeks following study entry
Secondary outcomes (7)
Minimum Trough Concentration (Ctrough) of Lopinavir
Count (%) of participants with minimum trough concentration (Ctrough) of steady-state Lopinavir >= 1 ug/mL
Measured: Measured 0, 1, 2, 4, 8, and 12 hours post-dose on 1, 4, 8, 12, 16, 24, 36 and 48 weeks following study entry
Free Fraction of LPV at Hour 2 Post Dose
Free fraction of steady-state lopinavir at 2 hours post dose
Measured: Weeks 1, 12 and 24
Change in HIV Viral Load From Baseline
Change from baseline in plasma HIV RNA viral load
Measured: Weeks 0, 12, 24, 36 and 48
HIV Viral Load <400 Copies/mL
Count (%) of participants with plasma HIV RNA viral load <400 copies/mL
Measured: Baseline and weeks 12, 24, and 48
Change in CD4 Percent
Change in CD4 percent from baseline
Measured: Weeks 0, 12, 24, 36 and 48
Change in WHO Weight-for-height Z-score
Change in WHO weight-for-height Z-score from entry. A Z-score indicates the number of standard deviations the measurement is away from the mean. A Z-score of 0 is equal to the mean of the reference population. Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population. The reference population was determined by the World Health Organization for children from 0 up to 5 years.
Measured: Weeks 0, 24, and 48
Change in Mid-upper Arm Circumference
Change in mid-upper arm circumference (MUAC) from entry
Measured: Weeks 0, 24, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2013 (estimated)
- Study start26 Oct 2015
- Primary completion11 Apr 2017
- Study completion29 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV PositiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Maxensia O Owor, MBChB, MMED, MPH, Study chair, International Maternal Pediatric Adolescent AIDS Clinical Trials Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01818258
- Sponsor's protocol ID
- IMPAACT P1092
- Other IDs
- U01AI068632, 11689
- Status last verified
- Jul 2021
- First submitted
- 14 Jan 2013
- Last updated
- 12 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data."
Publications
Owor M, Tierney C, Ziemba L, Browning R, Moye J, Graham B, Reding C, Costello D, Norman J, Wiesner L, Hughes E, Whalen ME, Purdue L, Mmbaga BT, Kamthunzi P, Kawalazira R, Nathoo K, Bradford S, Coletti A, Aweeka F, Musoke P. Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092. Pediatr Infect Dis J. 2021 May 1;40(5):446-452. doi: 10.1097/INF.0000000000003055.
PubMed 33464021Bwakura-Dangarembizi M, Ziemba L, Tierney C, Reding C, Bone F, Bradford S, Costello D, Browning R, Moye J, Vhembo T, Ngocho JS, Mallewa M, Chinula L, Musoke P, Owor M. Micronutrients and nutritional status among children living with HIV with and without severe acute malnutrition: IMPAACT P1092. BMC Nutr. 2023 Nov 2;9(1):121. doi: 10.1186/s40795-023-00774-1.
PubMed 37919816