Effectiveness of generic split adult tablets and paediatric fixed dose combination (FDC) of d4T/3TC/NVP in the treatment of HIV infected Malawian children

ISRCTN	ISRCTN55748789
DOI	https://doi.org/10.1186/ISRCTN55748789
Protocol serial number	394
Sponsor	Ministry of Health (Malawi) - HIV department
Funders	Ministry of Health (Malawi) - HIV department, Clinton Foundation (USA) - Malawi Country Office, German Agency for Technical Cooperation (Deutsche Gesellschaft für Technische Zusammenarbeit [GTZ]) (Germany) - Malawi Country Office, Private donor

Submission date: 12/05/2010
Registration date: 20/05/2010
Last edited: 17/03/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Ralf Weigel
Scientific

Lighthouse at Kamuzu Central Hospital
PO Box 106
Lilongwe
PO Box 106
Malawi

Phone	+265 (0)1 758 705
Email	r_weigel@lighthouse.org.mw

Study information

Primary study design	Interventional
Study design	Children with body weight 10kg and above: Open label, randomized controlled trial Children less than 10 kg body weight: Cohort study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effectiveness of generic split adult tablets and paediatric fixed dose combination (FDC) of d4T/3TC/NVP in the treatment of HIV infected Malawian children: A part open-label randomised controlled trial and part cohort study
Study acronym	TrioPed
Study objectives	We examine the effectiveness of standard paediatric 1st line ART regimens in Malawi in HIV infected children eligible for ART according to national guidelines. The aim of the study is examine the effectiveness of Triomune baby in children <10kg and compare effectiveness of split adult FDC of d4T/3TC/NVP (recommended 1st line paediatric regimen) with Triomune baby for children 10kg and above. Please note that as of 23/06/10 details of the extended ethics approval have been added to this record. More details can be found in the relevant field with the above update date.
Ethics approval(s)	1. National Health Sciences Research Committee (NHSRC), Lilongwe, Malawi, approved on the 7th of April 2008 (Protocol no: 394; approval valid until 16/3/2010) 2. Baylor College of Medicine, Houston, USA, approved on the 15th of May 2009 (Protocol no: H-23674; approval valid until 4/5/2011) Added 23/06/10: 3. National Health Sciences Research Committee (NHSRC), Lilongwe, Malawi extended their approval on the 17th of March 2010 (Protocol no: 394; approval valid until 16/03/11) Added 17/03/2011: Approvals extended: 1. Baylor College of Medicine approval valid from 18/02/2011 to 25/01/2012 2. National Health Sciences Research Committee (NHSRC) of Malawi valid from 15/03/2011 to 14/3/2012
Health condition(s) or problem(s) studied	Human Immunodeficiency Virus (HIV)
Intervention	Two different formulations of generic fixed dose combination of d4T/3TC/NVP tablets are compared in children 10kg and above: split adult tablets and a specific paediatric formulation (Triomune babyTM). Children less than 10kg bodyweight will be only started on Triomune baby.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	d4T/3TC/NVP (didehydrodeoxythymidine [d4T] / dideoxythiacytidine [3TC] / nevirapine [NVP]) - generic and Triomune®
Primary outcome measure(s)	Proportion of children with viral load of <400 copies/ml at 12 months follow-up
Key secondary outcome measure(s)	1. Monitoring patients' clinical response during routine visits 1.1. Change in body weight and height (z-scores) 1.2. Proportion of patients dying and lost to follow up 1.3. Time from enrolment to death and lost to follow up 1.4. Proportion of patients presenting with new symptoms and signs from enrolment 1.5. Proportion of patients requiring hospital admission 2. Monitoring patients' immunological response (CD4 count adjusted for age at entry, 3, 6, and 12 months) 2.1. Proportion of patients with immunological failure 2.2. Time until immunological failure occurs from enrolment 2.3. Change of Median CD4 percentage 3. Monitoring patients' virological response (HIV RNA at Entry, 3, 6, and 12 months) 3.1. Proportion of children with HIV RNA <400 copies/ml 3.2. Mean plasma viral load log10 change adjusted to baseline value 3.3. Proportion of patients with virological failure: 3.3.1. HIV RNA not suppressed to undetectable levels (<400 copies/ml) at 6 months or 3.3.2. Less then 10fold (1 log10) decrease from baseline viral load after 6 months of ART or 3.3.3. Repeated detection of HIV RNA in children who had <400 copies/ml 3.3.4. A reproducible increase in viral load of children who had an substantial virological response but still have low levels of detectable HIV RNA who then had an greater than 3fold (>0.5 log10) increase in copy number (children ≥ 2 years) 3.4. Time until virological failure occurs from enrolment 4. Monitoring Adverse Reactions 4.1. Signs and symptoms likely to be related to ART according to routine clinic checklist 4.2. Laboratory: 4.2.1. Complete Blood Count (CBC) 4.2.2. Aspartate Aminotransferase (AST) 4.2.3. Alanine Aminotransferase (ALT) 4.2.4. Lipase 4.2.5. Creatinine 4.3. Proportion of patients requiring modification of dosing regimen (e.g. prolonged lead in phase, intermittent stop) 4.4. Proportion of patients permanently stop/withdrawn from initial regimen and/or started on alternative 1st line regimen 5. Proportion of patients with >95% adherence by reported or observed pill count during clinic visits 6. Proportion of patients with >95% adherence with medication intake (ART) according to pill counts during unannounced home visits 7. Proportion of patients presenting in the clinic upon agreed appointment 8. Proportion of patients with detectable and undetectable NVP drug- plasma concentration in samples taken during pharmcokinetics (PK) study 9. Proportion of patients with NVP levels above the threshold at steady state 10. Proportion of patients having HIV drug resistance at baseline, 6 and 12 month, or when study treatment needs to be discontinued
Completion date	01/08/2011

Eligibility

Participant type(s)	Patient
Age group	Child
Upper age limit	15 Years
Sex	All
Target sample size at registration	410
Key inclusion criteria	1. Confirmed HIV infection (either HIV antibody test or, if <18 months, by HIV DNA test) 2. Caregiver and child, if applicable, counselled about HIV infection 3. Age <15 years 4. Body weight ≥3kg and <25kg 5. Informed consent given by caregiver and child if applicable 6. Eligible to start Anti-Retroviral Therapy (ART) according to Malawi National ART guidelines (3rd edition 2008) 7. Likely to comply with the study protocol (e.g. a main caregiver, responsible for administrating medication has been identified, caregiver and child have undergone an ART education session using the national paediatric ART education flipchart to understand the implications of ART, patient lives within the Lilongwe district)
Key exclusion criteria	1. Previous exposure to ART except Prevention of Mother-To-Child Transmission (PMTCT) 2. Patient requires hospital admission according to assessment of study clinician 3. Obvious liver disease on clinical examination (e.g. jaundice) 4. Obvious renal disease on clinical examination (e.g. lid oedema, hypertension)
Date of first enrolment	01/05/2008
Date of final enrolment	01/08/2011

Locations

Countries of recruitment

Malawi

Study participating centre

Lighthouse at Kamuzu Central Hospital

Lilongwe
PO Box 106
Malawi

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes