Strategies to Reduce Mortality Among HIV-infected and HIV-exposed Children Admitted With Severe Acute Malnutrition

HIV-1-infection Clinical Trial

— REDMOTHIV  

Official title:

A Randomized Trial to Investigate Strategies to Reduce Mortality Among HIV-infected and HIV-exposed Children Admitted With Severe Acute Malnutrition in Mulago Hospital, Kampala, Uganda

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05051163
• Other study ID #: REC.REF.2020-165
• Secondary ID: HS1277ES
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 14, 2021
• Est. completion date: June 14, 2024

Study information

• Verified date: September 2021
• Source: Makerere University
• Contact: Victor Musiime, PhD
• Phone: +256772401749
• Email: musiimev[@]yahoo.co.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among HIV-infected/HEU children admitted to Mwanamugimu Nutrition Unit, Mulago Hospital, Kampala, Uganda.

Description:

Background

HIV-infected and HIV-exposed-uninfected children (HEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in those that are HIV-infected. Preliminary audits at the Mwanamugimu Nutrition Unit, Mulago Hospital, in 2014 showed that 43% of the severely malnourished children that died were HIV-infected/HEU, despite only 30% of admissions being HIV-infected/HEU, with deaths due to infections in 90% of cases.

Objectives

This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among HIV-infected/HEU children admitted to Mwanamugimu Nutrition Unit. Secondary objectives include: comparing length of hospitalization, weight-for-height, weight-for-age and height-for-age z-scores between ceftriaxone versus standard of care (ampicillin and gentamicin) treatment arms; ascertaining the pattern/antimicrobial sensitivity of pathogens among participants; determining the prevalence and factors associated with HIV-infection among severely malnourished children; and evaluating the pharmacokinetics (PK) of lopinavir/ritonavir (LPV/r) among severely malnourished HIV-infected children.

Methods

This will be an open label randomized controlled trial involving 300 children; 76 HIV-infected (current mortality - 33%) and 224 HEU (current mortality - 26%). The participants will be randomized to receive 1week of ceftriaxone (n= 150) or standard-of-care (ampicillin/gentamicin) (n=150), in addition to other routine care; the ratio of HIV-infected to HEU (1:3) in this sample is reflective of the current proportions of the HIV-infected and HEU children admitted at Mwanamugimu Nutrition Unit. The trial's primary outcome will be in hospital mortality. 300 randomised children provides >80% power to detect reductions in mortality from the expected 28% to 14%, allowing for 10% noncompliance/lost-to-follow-up in each group. Secondary outcomes will be: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. 280 children provide 80% power to determine the prevalence of HIV-infection. Furthermore, all the HIV-infected children on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) 0-12h, maximum concentration (Cmax) and concentration at 12 hours after dose (C12h)] will be determined. The PK parameters (AUC 0-12h, Cmax, C12) will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 14, 2024
• Est. primary completion date: June 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 59 Months

Eligibility

Inclusion Criteria:

1. HIV-infected children aged 1 to 59 months admitted at Mwanamugimu Nutrition Unit with severe acute malnutrition

2. HIV exposed but uninfected children aged 1 to 59 months admitted at Mwanamugimu Nutrition Unit with severe acute malnutrition

3. For prevalence of HIV-infection sub-study, children presenting with severe acute malnutrition on admission at Mwanamugimu Nutrition Unit.

4. For PK sub-study, the child should have been on antiretroviral therapy for at least 2weeks and should have been in hospital for at least 2weeks.

Exclusion Criteria:

• For PK sub-study; a child with documented poor adherence to antiretroviral therapy.

• For PK sub-study; a child known to have vomited the drug on the sampling day.

Related Conditions & MeSH terms

• Child Nutrition Disorders
• HIV-1-infection
• Malnutrition
• Malnutrition, Child
• Severe Acute Malnutrition

Intervention

Drug:
• Ceftriaxone Sodium
7 days of once daily dosing
• Ampicillin
7 days of 6 hourly dosing
• Gentamicin
7 days of once daily dosing

Locations

Country	Name	City	State
Uganda	Makerere University College of Health Sciences	Kampala	Central

Sponsors (1)

Lead Sponsor	Collaborator
Makerere University

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In hospital mortality	Cumulative incidence	4 weeks
Secondary	Length of hospitalization	Number of days	90 days
Secondary	Weight-for-height z-score	Change from baseline	90 days
Secondary	Weight-for-age z-score	Change from baseline	90 days
Secondary	Height-for-age z-score	Change from baseline	90 days
Secondary	Pattern and antimicrobial sensitivity of pathogens	Frequency	7 days
Secondary	HIV infection	Prevalence	Baseline
Secondary	Area under the curve (AUC 0- 12h)	Geometric means	12hours
Secondary	Maximum concentration (Cmax)	Geometric means	12hours
Secondary	Concentration at 12hours post dose (C12h)	Geometric means	12hours