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Comparing Azithromycin to Amoxicillin in the Management of Uncomplicated Severe Acute Malnutrition in Burkina Faso: A Pilot Randomized Trial

Kieran S. O’BrienFrancis I Proctor Foundation, University of California, San Francisco, California;

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Ali SiéCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso;

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Clarisse DahCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso;

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Millogo OurohiréCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso;

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Moussa OuedraogoCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso;

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Valentin BoudoCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso;

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Ahmed ArzikaCentre de Recherche et Interventions en Santé Publique, Niamey, Niger;

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Elodie LebasFrancis I Proctor Foundation, University of California, San Francisco, California;

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Fanice NyatigoFrancis I Proctor Foundation, University of California, San Francisco, California;

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William GodwinFrancis I Proctor Foundation, University of California, San Francisco, California;

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J. Daniel KellyFrancis I Proctor Foundation, University of California, San Francisco, California;

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Benjamin F. ArnoldFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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Catherine E. OldenburgFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology & Biostatistics, University of California, San Francisco, California

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ABSTRACT.

Azithromycin is a promising alternative to amoxicillin in the management of uncomplicated severe acute malnutrition (SAM) as it can be administered as a single dose and has efficacy against several pathogens causing infectious disease and mortality in children under 5. In this pilot trial, we aimed to establish the feasibility of a larger randomized controlled trial and provide preliminary evidence comparing the effect of azithromycin to amoxicillin on weight gain in children with uncomplicated SAM. We enrolled children 6–59 months old with uncomplicated SAM at six healthcare centers in Burkina Faso. Participants were randomized to a single dose of azithromycin or a 7-day course of amoxicillin and followed weekly until nutritional recovery and again at 8 weeks. Apart from antibiotics, participants received standard of care, which includes ready-to-use therapeutic food. Primary feasibility outcomes included enrollment potential, refusals, and loss to follow-up. The primary clinical outcome was weight gain (g/kg/day) over 8 weeks. Outcome assessors were masked. Between June and October 2020, 312 children were screened, 301 were enrolled with zero refusals, and 282 (93.6%) completed the 8-week visit. Average weight gain was 2.5 g/kg/day (standard deviation [SD] 2.0) in the azithromycin group and 2.6 (SD 1.7) in the amoxicillin group (mean difference −0.1, 95% CI −0.5 to 0.3, P = 0.63). Fewer adverse events were reported in the azithromycin group (risk ratio 0.50, 95% CI 0.31–0.82, P = 0.006). With strong enrollment and follow-up, a fully powered trial in this setting is feasible.

Author Notes

Address correspondence to Catherine E. Oldenburg, Francis I. Proctor Foundation, University of California, San Francisco, 490 Illinois St., 2nd floor, San Francisco, CA 94158. E-mail: catherine.oldenburg@ucsf.edu

Financial support: This work was supported by the National Institutes of Health—National Institute of Child Health and Development (R21HD100932) and a UCSF REAC award. The funders reviewed the study design and had no role in the conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.

Authors’ addresses: Kieran S. O’Brien, Elodie Lebas, Fanice Nyatigo, William Godwin, and J. Daniel Kelly, Francis I Proctor Foundation, University of California, San Francisco, CA, E-mails: kieran.obrien@ucsf.edu, elodie.lebas@ucsf.edu, fanice.nyatigo@ucsf.edu, wgodwinner@gmail.com, and dan.kelly@ucsf.edu. Ali Sié, Clarisse Dah, Ourohiré Millogo, Moussa Ouedraogo, and Valentin Boudo, Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso, E-mails: sieali@yahoo.fr, n.clarissedah@yahoo.fr, ourohire2001@yahoo.fr, moussaoued0202@gmail.com, and valentinboudo@gmail.com. Ahmed Arzika, Centre de Recherche et Interventions en Santé Publique, Niamey, Niger, E-mail: ahmedarzika@gmail.com. Benjamin F. Arnold, Francis I Proctor Foundation, University of California, San Francisco, CA, and Department of Ophthalmology, University of California, San Francisco, CA, E-mail: ben.arnold@ucsf.edu. Catherine E. Oldenburg, Francis I Proctor Foundation, University of California, San Francisco, CA, Department of Ophthalmology, University of California, San Francisco, CA, and Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, E-mail: catherine.oldenburg@ucsf.edu.

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