Azithromycin for Uncomplicated Severe Acute Malnutrition in Burkina Faso (Pilot) (SAM)

Azithromycin as Adjunctive Therapy for Uncomplicated Severe Acute Malnutrition:

This pilot study is a randomized controlled trial designed to test the effect of the administration of adjunctive azithromycin in conjunction with standard outpatient treatment for uncomplicated severe acute malnutrition (SAM) in children aged 6-59 months. Children presenting to nutritional programs in Burkina Faso who meet eligibility criteria will be randomized to a single dose of oral azithromycin or a 7-day course of amoxicillin (standard of care) upon admission into the program. All enrolled children will receive ready-to-use therapeutic foods (RUTF). Enrolled children will be followed at each weekly clinic follow-up visit up to 8 weeks following admission. Data on anthropometric indicators, vital status, and adverse events will be collected during follow-up. Nutritional recovery over the 8-week study period will be compared by arm.

Study Overview

• Status: Completed
• Conditions: Uncomplicated Severe Acute Malnutrition
• Intervention / Treatment: Drug: Azithromycin; Drug: Amoxicillin

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 3

Contacts and Locations

Study Locations

• Burkina Faso
  • Boucle Du Mouhoun
    • Nouna, Boucle Du Mouhoun, Burkina Faso
      • Centre de recherche en Santé de nouna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 6-59 months
• WHZ <-3 SD or MUAC <115 mm
• No nutritional edema
• Able and willing to participate in full 8-week study
• Has not been admitted to a nutritional program for the treatment of SAM in the 3 preceeding months
• No antibiotic use in past 7 days
• No clinical complications requiring inpatient treatment (except for routine admission for children <6 months)
• No congenital abnormality or chronic debilitating illness that would lead to predictable growth faltering or reduce likelihood of SAM treatment benefit (such as cerebral palsy, Down syndrome, congenital heart disease, cleft lip/palate, etc)
• No allergy to macrolides/azalides
• Sufficient appetite according to a feeding test with ready-to-use therapeutic food (RUTF)
• Appropriate consent from at least one parent or guardian

Exclusion Criteria:

• Age <6 months or >59 months
• WHZ ≥-3 SD or MUAC ≥115 mm
• Nutritional edema
• Not able or willing to participate in full 8-week study
• Admission to a nutritional program for the treatment of SAM in the 3 preceeding months
• Antibiotic use in past 7 days
• Clinical complications requiring inpatient treatment
• Congenital abnormality or chronic debilitating illness that would lead to predictable growth faltering or reduce likelihood of SAM treatment benefit (such as cerebral palsy, Down syndrome, congenital heart disease, cleft lip/palate, etc)
• Allergy to macrolides/azalides
• Insufficient appetite according to a feeding test with ready-to-use therapeutic food (RUTF)
• Parent or guardian refuses to provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azithromycin; children in this arm will receive one dose of azithromycin	Drug: Azithromycin; Children enrolled in the trial and randomized to azithromycin will receive a single directly observed dose of oral azithromycin at 20 mg/kg up to the maximum adult dose of 1 g. Oral azithromycin will be administered at the time of enrollment. Enrolled children will also receive RUTF.; Other Names: Zithromax
Active Comparator: Amoxicillin; Children in this arm will receive a 7 day course of amoxicillin (standard of care)	Drug: Amoxicillin; Children enrolled in the trial and randomized to azithromycin will receive a 7-day course of oral amoxcillin given in twice-daily doses of 50-100 mg/kg, per the Burkina Faso guidelines for the management of severe acute malnutrition. The first dose will be administered at the time of enrollment and the remaining dose will be administered by the caregiver at home. Enrolled children will also receive RUTF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain	Weight will be measured at all follow-up time points and weight gain will be calculated at 8 weeks	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional Recovery - Primary Definition	Nutritional recovery is defined as, depending on admission criteria: weight-for-height/length is equal to or more than -2 Z-score and the child have had no oedema for at least 2 weeks, or the mid-upper-arm circumference is equal to or more than 125 mm and the child have had no oedema for at least 2 weeks. Anthropometric outcomes were defined according to the 2006 World Health Organization's Child Growth Standards: Stunted is length/height-for-age below the -2 z-score line. Severely stunted is below the -3 z-score line	8 weeks
Nutritional Recovery - Secondary Definition	Summarize the cumulative proportion recovered by arm. Children are considered recovered if they had mean upper arm circumference > 12.5 or weight-for-height/length > -2 for 2 consecutive measurements. Additionally, it includes children who had had mean upper arm circumference >12.5 or weight-for-height/length > -2 on their final measurement, regardless of whether they met these criteria on the previous visit.	8 weeks
Malaria	Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to determine malaria infection status.	8 weeks
Mortality	Vital status will be assessed at all follow-up time points and mortality will be defined as death during the study period.	8 weeks
Length/Height-for-age Z-score (LAZ/HAZ)	Height or length will be measured at all follow-up time points and height-for-age z-scores will be calculated. A z-score of 0 represents the population mean. The z-score will be positive if the data value lies above the mean, and negative if the data value lies below the mean. Anthropometric outcomes were defined according to the 2006 World Health Organization's Child Growth Standards: Stunted is length/height-for-age below the -2 z-score line. Severely stunted is below the -3 z-score line	8 weeks
Mid-Upper Arm Circumference (MUAC)	Mid-upper arm circumference will be measured at all follow-up time points	8 weeks
Weight-for-Age Z-scores (WAZ)	Weight will be measured at all follow-up time points and weight-for-age z-scores will be calculated. A z-score of 0 represents the population mean. The z-score will be positive if the data value lies above the mean, and negative if the data value lies below the mean. Anthropometric outcomes were defined according to the 2006 World Health Organization's Child Growth Standards: Underweight is weight-for-age below the -2 z-score line. Severely underweight is below the -3 z-score line.	8 weeks
Weight-for-Height Z-score (WHZ)	Weight and height, assessed at all follow-up time points, will be used to calculate weight-for-height z-scores. A z-score of 0 represents the population mean. The z-score will be positive if the data value lies above the mean, and negative if the data value lies below the mean. Anthropometric outcomes were defined according to the 2006 World Health Organization's Child Growth Standards: Overweight is weight-for-length/height above the 2 z-score line. Severely overweight; weight-for-length/height above the 3 z-score line	8 weeks
Intestinal Microbiome	baseline and 8 week intestinal microbiome will be compared between the 2 arms alpha diversity using inverse Simpson's index and Shannon's index, expressed in effective number. The Shannon Diversity Index is a quantitative measure that reflects how many different bacterial species there are in a sample. The greater the index, the more diverse the gut microbiota. An index of 0 indicates a community that only has one species. A negative change indicates a decrease in diversity and a positive change indicates an increase in diversity. The Simpson's Diversity Index is a measure of diversity which takes into account the number of species present, as well as the relative abundance of each species. As species richness and evenness increase, so diversity increases. The value ranges between 0 and 1, where 1 represents infinite diversity and 0, no diversity.	Baseline, 8 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Centre de Recherche en Sante de Nouna, Burkina Faso
• Investigators: Principal Investigator: Catherine E Oldenburg, ScD, University of California, San Francisco

Publications and helpful links

General Publications

• Oldenburg CE, Hinterwirth A, Ourohire M, Dah C, Ouedraogo M, Sie A, Boudo V, Chen C, Ruder K, Zhong L, Lebas E, Nyatigo F, Arnold BF, O'Brien KS, Doan T. Gut Resistome after Antibiotics among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial. Am J Trop Med Hyg. 2022 Jun 13;107(1):59-64. doi: 10.4269/ajtmh.22-0007. Print 2022 Jul 13.
• Sie A, Dah C, Ourohire M, Ouedraogo M, Boudo V, Arzika AM, Lebas E, Nyatigo F, Arnold BF, O'Brien KS, Oldenburg CE. Azithromycin versus Amoxicillin and Malarial Parasitemia among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial. Am J Trop Med Hyg. 2021 Sep 27;106(1):351-355. doi: 10.4269/ajtmh.21-0595.
• O'Brien KS, Sié A, Dah C, Ourohire M, Arzika AM, Boudo V, Lebas E, Godwin WW, Arnold BF, Oldenburg CE. Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2021 Apr 20;7(1):97. doi: 10.1186/s40814-021-00836-w.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Actual): December 25, 2020
• Study Completion (Actual): December 25, 2020

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Severe Acute Malnutrition; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin; Azithromycin
• Other Study ID Numbers: 18-25274; 1R21HD100932-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes