Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial

Kieran S O’Brien,Clarisse Dah,Catherine E Oldenburg,William W Godwin,Ahmed M Arzika,Benjamin F Arnold,Valentin Boudo,Ali Sié,Millogo Ourohire,Elodie Lebas

doi:10.1186/s40814-021-00836-w

Abstract

BackgroundGiven the high risk of infectious mortality among children with severe acute malnutrition (SAM), the World Health Organization recommends routine administration of a broad-spectrum antibiotic like amoxicillin as part of the management of uncomplicated SAM. However, evidence for the efficacy of amoxicillin to improve nutritional recovery or reduce mortality has been mixed. With a long half-life and evidence of efficacy to reduce mortality in high-risk populations, azithromycin is a potential alternative to amoxicillin in the management of SAM. In this pilot study, we aim to compare the efficacy of azithromycin to amoxicillin to improve nutritional outcomes in children with uncomplicated SAM.MethodsThis pilot randomized controlled trial will enroll 300 children with uncomplicated SAM from 6 Centre de Santé et de Promotion Sociale in the Boromo health district in Burkina Faso. Eligible children are randomized to receive a single directly observed dose of oral azithromycin or a 7-day course of oral amoxicillin in addition to the standard package of care for uncomplicated SAM. Enrolled children are followed weekly until nutritional recovery, and all children return for a final study visit at 8 weeks after enrollment. Anthropometric indicators, vital status, and clinical outcomes are monitored at each visit and compared by arm. Primary feasibility outcomes include enrollment potential, refusals, loss to follow-up, and completeness of data collection. The primary clinical outcome is weight gain (g/kg/day) over the 8-week study period.DiscussionThis pilot trial will establish the feasibility of conducting a full-scale randomized controlled trial to evaluate alternative antibiotics in this setting and provide preliminary evidence for the efficacy of azithromycin compared to amoxicillin to improve outcomes for children with SAM.Trial registrationThis trial was first registered on clinicaltrials.gov on 26 June 2018 (NCT03568643).

Highlights

Given the high risk of infectious mortality among children with severe acute malnutrition (SAM), the World Health Organization recommends routine administration of a broad-spectrum antibiotic like amoxicillin as part of the management of uncomplicated SAM
With a high risk of infectious mortality, children with SAM stand to benefit from antibiotics, yet evidence on the impact of standard-of-care amoxicillin on mortality and nutritional outcomes is mixed
Azithromycin is a potential alternative to amoxicillin that could be administered as a single dose, obviating the need to rely on caregiver dosing over time

Summary

Introduction

Given the high risk of infectious mortality among children with severe acute malnutrition (SAM), the World Health Organization recommends routine administration of a broad-spectrum antibiotic like amoxicillin as part of the management of uncomplicated SAM. With a long half-life and evidence of efficacy to reduce mortality in high-risk populations, azithromycin is a potential alternative to amoxicillin in the management of SAM In this pilot study, we aim to compare the efficacy of azithromycin to amoxicillin to improve nutritional outcomes in children with uncomplicated SAM. A third study of daily cotrimoxazole for children recovering from complicated SAM found no benefit for nutritional recovery or mortality [5] These conflicting results may indicate that empiric antibiotic therapy for uncomplicated SAM is unnecessary in some settings or that a different antibiotic class is needed

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