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

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

doi:10.1186/s40814-021-00836-w

Cited by 6 publications

(10 citation statements)

References 13 publications

(12 reference statements)

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“…[31][32][33] A pilot trial in Burkina Faso testing the efficacy of azithromycin to improve nutritional outcomes in children with uncomplicated severe acute malnutrition has recently completed recruitment. 34 With regard to secondary outcomes, the difference in the composite outcome of hospitalization or death merits consideration. There was a 21% lower risk of hospitalization or death in the 90-day follow-up period in the azithromycin group.…”

Section: Discussionmentioning

confidence: 99%

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Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings

et al. 2021

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IMPORTANCEWorld Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. OBJECTIVE To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. DESIGN, SETTING, AND PARTICIPANTS The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. INTERVENTIONS Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. MAIN OUTCOMES AND MEASURES Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. RESULTS A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and −0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. CONCLUSIONS AND RELEVANCEThe study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin (continued) Key Points Question Does the addition of azithromycin to the standard case management of acute watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished reduce mortality and improve linear growth? Findings This randomized clinical trial of 8266 children was unable to detect a survival benefit for children from the addition of azithromycin to the standard World Health Organization (WHO) case management of acute wat...

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Section: Discussionmentioning

confidence: 99%

“… 31 , 32 , 33 A pilot trial in Burkina Faso testing the efficacy of azithromycin to improve nutritional outcomes in children with uncomplicated severe acute malnutrition has recently completed recruitment. 34 …”

Section: Discussionmentioning

confidence: 99%

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings

et al. 2021

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“…Complete methods for the trial have been previously reported (O'Brien, Sié, Dah, Ourohire, Arzika, et al, 2021;O'Brien, Sie, Dah, Ourohire, Ouédraogo, et al, 2021) Participants were recruited via outpatient nutritional programmes at six primary health care facilities in Boromo District, Burkina Faso from June through October 2020.…”

Section: Study Settingmentioning

confidence: 99%

“…Response to treatment for outpatient SAM may be different for children admitted based on different criteria given that these criteria identify different subpopulations of children. We utilized data from a randomized controlled trial of azithromycin compared with amoxicillin for outpatient management of SAM (O'Brien, Sié, Dah, Ourohire, Arzika, et al, 2021 ) to evaluate response to treatment in children admitted to outpatient nutritional programmes based on low MUAC, low WHZ, or low MUAC and WHZ. We further evaluated outcomes in children with low WAZ and height‐for‐age Z ‐score (HAZ) at enrolment, as these markers may be useful in identifying the highest‐risk children who may benefit from admission to a nutritional programme.…”

Section: Introductionmentioning

confidence: 99%

“…Data arose from a randomized controlled trial of azithromycin versus amoxicillin for SAM. All measurements were standardized and taken by trained anthropometrists as part of the trial, but the sample size was limited by the trial's overall objective(O'Brien, Sié, Dah, Ourohire, Arzika, et al, 2021;O'Brien, Sie, Dah, Ourohire, Ouédraogo, et al, 2021). CIs were wide for someMid-upper arm circumference (MUAC; a), weight-for-height Z-score (WHZ; b), weight-for-age Z-score (WAZ; c), and height-forage Z-score (HAZ; d) over time by criteria used for admission to the outpatient nutritional programme.…”

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How does baseline anthropometry affect anthropometric outcomes in children receiving treatment for severe acute malnutrition? A secondary analysis of a randomized controlled trial

Dah

Millogo

Sié

et al. 2022

Maternal & Child Nutrition

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Mid-upper arm circumference (MUAC) < 11.5 cm and weight-for-height Z-score (WHZ) < −3 are used for screening for severe acute malnutrition (SAM). Underweight and concurrent wasting and stunting may better target those at the highest risk of mortality. We compared anthropometric outcomes in children enrolled in a trial of antibiotics for SAM based on categories of baseline anthropometry, including indicators for programme admission (WHZ < −3, MUAC < 11.5) and alternative indicators (weight-forage Z-score [WAZ] < −3, concurrent wasting and stunting [WHZ < −3 and height-for-age Z-score < −3]). Participants were followed weekly until nutritional recovery and at 8 weeks. We evaluated changes in weight gain (g/kg/day), MUAC, and WHZ in children admitted by admissions criteria (MUAC only, WHZ only, or MUAC and WHZ) and by underweight or concurrent wasting and stunting. Of 301 admitted children, 100 (33%) were admitted based on MUAC only, 41 (14%) WHZ only, and 160 (53%) both MUAC and WHZ, 210 (68%) were underweight and 67 (22%) were concurrently wasted/stunted. Low MUAC and low WHZ children had the lowest probability of nutritional recovery (17% vs. 50% for MUAC-only and 34% for WHZ-only). There was no difference in weight gain velocity or WHZ by admissions criteria (WHZ and/or MUAC). Underweight and concurrently wasted/stunted children had lower MUAC and WHZ at 8 weeks compared with those who were not underweight or concurrently wasted and stunted. Children with both low MUAC and low WHZ had the worst outcomes. Relying on MUAC alone may miss children who have poor outcomes. Other indicators, such as WAZ, may be useful for identifying vulnerable children.

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Azithromycin versus Amoxicillin and Malarial Parasitemia among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial

Sié

Dah

Millogo

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Antibiotics are recommended by the WHO as part of the management of uncomplicated severe acute malnutrition in children. We evaluated whether azithromycin, an antibiotic with antimalarial properties, improved malarial parasitemia outcomes in children with severe acute malnutrition compared with amoxicillin, an antibiotic commonly used for severe acute malnutrition that does not have antimalarial properties. Total of 301 children were randomized (1:1) to a single oral dose of azithromycin or a 7-day course of amoxicillin and followed for 8 weeks. We found no significant evidence that children receiving azithromycin had improved parasitemia outcomes relative to amoxicillin. Although azithromycin may have advantages over amoxicillin in terms of dosing and administration for uncomplicated severe acute malnutrition, it may not yield additional benefit for malaria outcomes.

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

Cited by 6 publications

References 13 publications

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings

How does baseline anthropometry affect anthropometric outcomes in children receiving treatment for severe acute malnutrition? A secondary analysis of a randomized controlled trial

Azithromycin versus Amoxicillin and Malarial Parasitemia among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial

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