Children with human immunodeficiency virus (HIV) in Africa, pharmacokinetics adn acceptability/adherence of simple antiretroviral regimen (CHAPAS-3)

• Register: PACTR
• Last refreshed on: 29 April 2013
• Main ID: PACTR201006000222401
• Date of registration: 15/06/2010
• Primary sponsor: Medical Research Council - Clinical Trials Unit
• Public title: Children with human immunodeficiency virus (HIV) in Africa, pharmacokinetics adn acceptability/adherence of simple antiretroviral regimen (CHAPAS-3)
• Scientific title: A randomised trial to compare toxicity and pharmacokinetics of three fixed-dose combination based antiretroviral regimens for treatment of human immunodeficiency virus (HIV) infected children in Africa
• Date of first enrolment: 2010-10-18
• Target sample size: 420
• Recruitment status: Open to recruitment: actively recruiting participa
• URL: HTTP://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?da=true&tno=PACTR201006000222401
• Study type: interventional
• Study design: Parallel: different groups receive different interventions at same time during study,; Randomised,; Stratified allocation, Randomisation will be stratified by centre, treatment history and choice of NNTRI, in Zambia it will additionally be stratified by age,; Within strata randomisation lists will be prepared using the urn method. A randomisation list will be securely incorporated within the trial database, held at a local trials centre for each clinical centre, and randomisations will be performed locally.,

Countries of recruitment

South Africa

Contacts

• Name: Margaret Thomasson
• Affiliation: Medical Research Council, UK

• Name: Veronica Mulenga
• Affiliation: CHAPAS 3 Project Coordinator

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age one month to 13 years, either sex
1.1 ART naive children in Uganda being randomised to commence therapy on a d4T based regimen must be 0 - 4 years old in accordance with local guidelines
1.2 ART experienced chidlren being randomised to continue therapy on d4T based regimen must be 5yr or older with no clincial symptoms of lipodystrophy. If symptoms of severe lipodystropy then will switch to another regimen.
2. Weighing greater than 3kg and less than 25kg (heavier children should receive adult tablets and not be enrolled in CHAPAS-3)
3. Participants must have a confirmed diagnosis of HIV-1 infection
4. Parents or guardians, and children where appropriate accordign to age and knowledge of HIV status, must be willing adn bale to give informed consent for randomisation to first-line ART strategy and participation in the PK substudy if eligible
5.1 ART naive (except for exposure to perinatal ART for the prevention of mother to child HIV transmission), meeting World Health Organization (WHO)or national (WHO modified) criteria for initiating therapy and ready to start initial 2NRTI+NNRTI based regimen according to local guidelines (i.e., according to WHO stage/CD4 and guielines concerning first-line ART in children who have been exposed to NVP perinatally) or
5.2 Currently taking d4T based regimen for at least 2 years with screenign HIV RNA viral load less than 50 copies/ml, no history of recieving other ARV drugs and CD4 count and/or CD4 percent stable over the previous 6 months
6. Able and willing to take each of the possible regimens
Exclusion criteria: 1. Cannot or unlikely to attend regularly (e.g. usual residence too far from study centre)
2. Likelihood of poor attendance
3. Presence of acute infection
4. In receipt of medication contraindicated by ART or on chemotherapy for malignancy. Children under three years of age receiving anti-tuberculosis therapy should not be enrolled ( as they will have to receive nevirapine)
5. Laboratory abnormalities which are a contra-indication for teh child to start ART/change to any of the possible 3 regimens
6. Being pregnant of breast-feeding an infant
7. Perinatal exposure to NVP (either through pMTCT or breastfeeding) for children aged 3 - 6 months only

Age minimum: 1 Month
Age maximum: 13 Year
Gender: Both

Health Condition(s) or Problem(s) studied

HIV/AIDS
null

Primary Outcome(s)

All Children, grade 2/3/4 clinical or grade 3 (confirmed) or 4 (any grade) laboratory adverse events

For PK substudies: Plasma pharmacokinetic parameters (AUC, Cmin, Cmax) of ABC, ZDV and 3TC in FDCs with or without NVP and EFV from the full PK curves

Secondary Outcome(s)

Acceptability of once versus twice daily dosing by carer questionnaire

Adherence as measured by electronic recording devices (MEMSCaps) clinic-based pill counts, carer and child questionnaire including visual analogue scale from randomisation

Anaemia, nuetropenia, lipodystrophy/lipoatrophy, mitochondrial disease, peripheral neuropathy and hypersensitivity reactions of any grade

Any AE leading to dose reduction or permanent/temporary interruption/substitution of ART

change in body circumferences

Change in CD4 and CD4 percent

Change in growth parameters (weight-for-age, height-for-age, weight-for-height)

Change in HIV RNA viral load and proportion of children with HIV RNA less than 50 and less than 400 copies/ml

Change in skinfold thickness

Changes in endothelial injury (functional and cellular) and inflammatory markers (D-Dimer, CRP, interleukin 6). Vascular function parameters (Intima Media Thickness (IMT) of the carotid artery) and pulse wave velocity, CECs and EMPs will be measured using portable equipment, by a single investigator in each site

clinical and or laboratory adverse events Grade 3 or 4, possibly or probably related to ABC, ZDV or d4T

Cost and cost effectiveness

Secondary ID(s)

ISRCTN69078957

Source(s) of Monetary Support

EDCTP

Health Research Board

Department for International Development (DfID)

The Ministerio de Sanidad y Consumo

Medical Research Council