Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial

Introduction Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dos...

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Main Authors: Catherine E Oldenburg, Thuy Doan, Ali Sie, Lucienne Ouermi, Elodie Lebas, Mamadou Bountogo, Boubacar Coulibaly, Alphonse Zakane, Guillaume Compaoré, Michelle Hsiang, Benjamin Arnold, Fla Koueta, Kieran Sunanda O’Brien, Thierry A Ouedraogo, Adama Compaoré, Hadley R Burroughs, Ian Fetterman, Jessica L La Mons
Format: Article
Language:English
Published: BMJ Publishing Group 2025-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/7/e104591.full
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author Catherine E Oldenburg
Thuy Doan
Ali Sie
Lucienne Ouermi
Elodie Lebas
Mamadou Bountogo
Boubacar Coulibaly
Alphonse Zakane
Guillaume Compaoré
Michelle Hsiang
Benjamin Arnold
Fla Koueta
Kieran Sunanda O’Brien
Thierry A Ouedraogo
Adama Compaoré
Hadley R Burroughs
Ian Fetterman
Jessica L La Mons
author_facet Catherine E Oldenburg
Thuy Doan
Ali Sie
Lucienne Ouermi
Elodie Lebas
Mamadou Bountogo
Boubacar Coulibaly
Alphonse Zakane
Guillaume Compaoré
Michelle Hsiang
Benjamin Arnold
Fla Koueta
Kieran Sunanda O’Brien
Thierry A Ouedraogo
Adama Compaoré
Hadley R Burroughs
Ian Fetterman
Jessica L La Mons
author_sort Catherine E Oldenburg
collection DOAJ
description Introduction Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.Methods and analysis This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score <−3 SD and/or mid-upper arm circumference <115 mm. Additionally, the children must not have received antibiotics in the past 7 days and have not received nutritional programme treatment for SAM in the 2 weeks before enrolling in the study. Each participant will receive a 7-day course of treatment or placebo based on the arm they were randomised to; 1 dose of azithromycin plus placebo for consistency in the number of doses, 7 days of amoxicillin or 7 days of placebo, with the first dose directly observed in all arms. The primary endpoint outcome will be weight gain defined by g/kg/day at 8 weeks. Mortality and relapse will be assessed at 8 weeks and 3 months, 6 months, 9 months and 12 months.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board at the University of California, San Francisco (Protocol 23–39411) and the Comité d’Ethique pour la Recherche en Santé in Ouagadougou, Burkina Faso (Protocol 2024-01-08). The results of this study will be disseminated to the Ministry of Health, community stakeholders and via peer-reviewed publications and academic conferences.Trial registration number NCT06010719.
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spelling doaj-art-448af97e5d634e30b195b9cbc5876e922025-08-20T03:30:36ZengBMJ Publishing GroupBMJ Open2044-60552025-07-0115710.1136/bmjopen-2025-104591Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trialCatherine E Oldenburg0Thuy Doan1Ali Sie2Lucienne Ouermi3Elodie Lebas4Mamadou Bountogo5Boubacar Coulibaly6Alphonse Zakane7Guillaume Compaoré8Michelle Hsiang9Benjamin Arnold10Fla Koueta11Kieran Sunanda O’Brien12Thierry A Ouedraogo13Adama Compaoré14Hadley R Burroughs15Ian Fetterman16Jessica L La Mons17Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USAFrancis I Proctor Foundation, University of California San Francisco, San Francisco, California, USACentre de Recherche en Sante de Nouna, Nouna, Burkina FasoCentre de Recherche en Sante de Nouna, Nouna, Burkina FasoFrancis I Proctor Foundation, University of California San Francisco, San Francisco, California, USACentre de Recherche en Sante de Nouna, Nouna, Burkina FasoCentre de Recherche en Sante de Nouna, Nouna, Burkina FasoCentre de Recherche en Sante de Nouna, Nouna, Burkina FasoCentre de Recherche en Sante de Nouna, Nouna, Burkina FasoMalaria Elimination Initiative, University of California San Francisco (UCSF), San Francisco, California, USAFrancis I Proctor Foundation, University of California San Francisco, San Francisco, California, USACentre Hospitalier Universitaire Pédiatrique Charles De Gaulle, Ouagadougou, Burkina FasoFrancis I Proctor Foundation, University of California San Francisco, San Francisco, California, USACentre de Recherche en Sante de Nouna, Nouna, Burkina FasoCentre de Recherche en Sante de Nouna, Nouna, Burkina FasoUniversity of California San Francisco, San Francisco, California, USAUniversity of California San Francisco, San Francisco, California, USAUniversity of California San Francisco, San Francisco, California, USAIntroduction Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.Methods and analysis This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score <−3 SD and/or mid-upper arm circumference <115 mm. Additionally, the children must not have received antibiotics in the past 7 days and have not received nutritional programme treatment for SAM in the 2 weeks before enrolling in the study. Each participant will receive a 7-day course of treatment or placebo based on the arm they were randomised to; 1 dose of azithromycin plus placebo for consistency in the number of doses, 7 days of amoxicillin or 7 days of placebo, with the first dose directly observed in all arms. The primary endpoint outcome will be weight gain defined by g/kg/day at 8 weeks. Mortality and relapse will be assessed at 8 weeks and 3 months, 6 months, 9 months and 12 months.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board at the University of California, San Francisco (Protocol 23–39411) and the Comité d’Ethique pour la Recherche en Santé in Ouagadougou, Burkina Faso (Protocol 2024-01-08). The results of this study will be disseminated to the Ministry of Health, community stakeholders and via peer-reviewed publications and academic conferences.Trial registration number NCT06010719.https://bmjopen.bmj.com/content/15/7/e104591.full
spellingShingle Catherine E Oldenburg
Thuy Doan
Ali Sie
Lucienne Ouermi
Elodie Lebas
Mamadou Bountogo
Boubacar Coulibaly
Alphonse Zakane
Guillaume Compaoré
Michelle Hsiang
Benjamin Arnold
Fla Koueta
Kieran Sunanda O’Brien
Thierry A Ouedraogo
Adama Compaoré
Hadley R Burroughs
Ian Fetterman
Jessica L La Mons
Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
BMJ Open
title Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
title_full Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
title_fullStr Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
title_full_unstemmed Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
title_short Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial
title_sort azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition amour study protocol for a double masked randomised controlled trial
url https://bmjopen.bmj.com/content/15/7/e104591.full
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