Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201006000222401 Date of Registration: 15/06/2010
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Children with human immunodeficiency virus (HIV) in Africa, pharmacokinetics adn acceptability/adherence of simple antiretroviral regimen (CHAPAS-3)
Official 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
Brief summary describing the background and objectives of the trial The CHAPAS-3 protocol describes an open-label three centre randomised phase II/III trial evaluating new solid, dispersible scored antiretroviral fixed dose combination and single drugs in African children. Specific objectives are to compare pharmacokinetics, toxicity, acceptability, adherence, virological efficacy and cost-effectiveness of three first line antiretroviral regimens in children 13 or younger, in both ART niave and in children with undetectable viral load who have recieved stavudine
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CHAPAS 3
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2010
Actual trial start date 18/10/2010
Anticipated date of last follow up 01/09/2013
Actual Last follow-up date
Anticipated target sample size (number of participants) 420
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
ISRCTN69078957 ISRCTN Register
ISRCTN69078957 ISRCTN Register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
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. Masking/blinding used
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. Masking/blinding used
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. Masking/blinding used
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. Masking/blinding used
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Arm d4T: d4T/3TC/NVP or d4T/3TC + EFV weight and age dependant and according to WHO paediatric antiretroviral therapy dosing charts 96 weeks Stavudine arm: d4T/3TC/NVP or d4T/3TC + EFV 140 Active-Treatment of Control Group
Experimental Group Arm ABC: ABC/3TC/NVP or ABC/3TC +EFV Weight and age dependant and according to WHO paediatric antiretroviral therapy dosing charts 96 weeks Abacavir arm: 2 arm ABC: ABC/3TC/NVP or ABC/3TC +EFV 140
Experimental Group ARM ZDV: ZDV/3TC/NVP or ZDV/3TC +EFV Weight and age dependant and according to WHO paediatric antiretroviral therapy dosing charts 96 weeks Zidovudine arm: ZDV/3TC/NVP or ZDV/3TC +EFV 140
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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 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 1 Month(s) 13 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/04/2010 University College London Research Ethics Committee (UCL, UK)
Ethics Committee Address
Street address City Postal code Country
c/o Graduate School, Norht Cloisters, Wilkins Building, Gower Street London WC E1 6BT United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/03/2010 Joint Clinical Research Centre IRB (Uganda)
Ethics Committee Address
Street address City Postal code Country
Plot 893, Ring Road, Butikiro House, Mengo Kampala Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/04/2010 University of Zambia, Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Zambia, School of Medicine, Ridgeway Campus Lusaka Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome All Children, grade 2/3/4 clinical or grade 3 (confirmed) or 4 (any grade) laboratory adverse events All children throughout the trial
Primary Outcome 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 PK substudy - at week 6
Secondary Outcome Change in skinfold thickness week 0 to 48 and 96 weeks (converted to age and sex-adjusted z-scores)
Secondary Outcome change in body circumferences week 0 to 48 and 96 weeks
Secondary Outcome clinical and or laboratory adverse events Grade 3 or 4, possibly or probably related to ABC, ZDV or d4T throughout trial period
Secondary Outcome Anaemia, nuetropenia, lipodystrophy/lipoatrophy, mitochondrial disease, peripheral neuropathy and hypersensitivity reactions of any grade throughout trial period
Secondary Outcome Any AE leading to dose reduction or permanent/temporary interruption/substitution of ART throughout trial period
Secondary Outcome 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 week 0 to 48 and 96 weeks
Secondary Outcome Adherence as measured by electronic recording devices (MEMSCaps) clinic-based pill counts, carer and child questionnaire including visual analogue scale from randomisation weeks 6, 12, 24, 36, 48 then 2 weekly until trial end
Secondary Outcome Acceptability of once versus twice daily dosing by carer questionnaire weeks 0, 6, 24, 48, then 2 weekly until tiral end
Secondary Outcome Change in HIV RNA viral load and proportion of children with HIV RNA less than 50 and less than 400 copies/ml weeks 0 to 48 and 96 (assayed retrospectively)
Secondary Outcome Cost and cost effectiveness end of trial
Secondary Outcome Change in CD4 and CD4 percent 0 to 48 and 96 weeks
Secondary Outcome Change in growth parameters (weight-for-age, height-for-age, weight-for-height) 0 to 48 and 96 weeks (converted to age and sex-adjusted z-scores)
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Baylor College of Medicine Children's Foundation Mulago Hospital PIDC, Ward 15, Clock Tower Mulago Uganda
Joint Clinical Research Centre PO Box 10005 Kampala Uganda
University Teaching Hospital Nationalist Rd, Ridgeway Lusaka 10101 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP The Hague Netherlands
EDCTP The Hague Netherlands
Medical Research Council United Kingdom
Medical Research Council United Kingdom
Department for International Development (DfID) United Kingdom
Department for International Development (DfID) United Kingdom
The Ministerio de Sanidad y Consumo Spain
The Ministerio de Sanidad y Consumo Spain
Health Research Board Ireland
Health Research Board Ireland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Medical Research Council - Clinical Trials Unit 222 Euston Road London NW1 2DA United Kingdom Charities/Societies/Foundation
Primary Sponsor Medical Research Council - Clinical Trials Unit 222 Euston Road London NW1 2DA United Kingdom Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Professor Diana Gibb MRC Clinical Trials Unit, 222 Euston Rd London NW1 2DA United Kingdom
Professor Diana Gibb MRC Clinical Trials Unit, 222 Euston Rd London NW1 2DA United Kingdom
Dr. Veronica Mulenga University Teaching Hospital, D Block, Department of Paediatrics and Child Health Lusaka 10101 Zambia
Dr. Veronica Mulenga University Teaching Hospital, D Block, Department of Paediatrics and Child Health Lusaka 10101 Zambia
Professor Chifumbe Chintu University Teaching Hospital, D Block, Department of Paediatrics and Child Health Lusaka 10101 Zambia
Professor Chifumbe Chintu University Teaching Hospital, D Block, Department of Paediatrics and Child Health Lusaka 10101 Zambia
Dr. Cissy Kityo Joint Clinical Research Centre, PO Box 10005 Kampala Uganda
Dr. Cissy Kityo Joint Clinical Research Centre, PO Box 10005 Kampala Uganda
Dr. Victor Musiime Joint Clinical Research Centre, PO Box 10005 Kampala Uganda
Dr. Victor Musiime Joint Clinical Research Centre, PO Box 10005 Kampala Uganda
Dr. Alice Asiimwe Rwego Baylor College fo Medicine, Bristol Meyers Squibb Children's Clinical Centre of Excellence, Block 5 Mulago Hospital PO Box 72052 Kampala Uganda
Dr. Alice Asiimwe Rwego Baylor College fo Medicine, Bristol Meyers Squibb Children's Clinical Centre of Excellence, Block 5 Mulago Hospital PO Box 72052 Kampala Uganda
Dr. David Burger Dept. of Clinical Pharmacy, 864 Radboud University Nijmegen Medical Center, Geert Grooteplein 10 Nijmegen 6525 GA Netherlands
Dr. David Burger Dept. of Clinical Pharmacy, 864 Radboud University Nijmegen Medical Center, Geert Grooteplein 10 Nijmegen 6525 GA Netherlands
Dr. Helen McIlleron, MBChB, PhD UNiversity of Cape Town, K-45 Old Main Building, Groote Schuur Hospital Observatory, Cape Town 7925 South Africa
Dr. Helen McIlleron, MBChB, PhD UNiversity of Cape Town, K-45 Old Main Building, Groote Schuur Hospital Observatory, Cape Town 7925 South Africa
Dr. Concepta Merry Makerere University, PO Box 7062 Kampala Uganda
Dr. Concepta Merry Makerere University, PO Box 7062 Kampala Uganda
Dr Sarah Walker 22 Euston Road London NW1 2DA United Kingdom
Dr Sarah Walker 22 Euston Road London NW1 2DA United Kingdom
Dr. Margaret Thomason 222 Euston Road London NW1 2DA United Kingdom
Dr. Margaret Thomason 222 Euston Road London NW1 2DA United Kingdom
Prof Addy Kekitiinwa Baylor College fo Medicine, Bristol Meyers Squibb Children's Clinical Centre of Excellence, Block 5 Mulago Hospital PO Box 72052 Kampala Uganda
Prof Addy Kekitiinwa Baylor College fo Medicine, Bristol Meyers Squibb Children's Clinical Centre of Excellence, Block 5 Mulago Hospital PO Box 72052 Kampala Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Diana M Gibb dmg@ctu.mrc.ac.uk +44 20 76704709 222 Euston Road
City Postal code Country Position/Affiliation
London NW12DA United Kingdom Medical Resarch Council - Clinical Trial Unit (UK)
Role Name Email Phone Street address
Public Enquiries Veronica Mulenga veromulenga@yahoo.co.uk 26 0211 254681 University Teaching Hospital, Department of Paediatrics and Child Health
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia CHAPAS 3 Project Coordinator
Role Name Email Phone Street address
Scientific Enquiries Margaret Thomasson mjth@ctu.mrc.ac.uk 44 20 7670 4615 222 Euston Road
City Postal code Country Position/Affiliation
London NW1 2DA United Kingdom Medical Research Council, UK
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information