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

Study Overview
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Brief Summary
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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.

Official Title
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Azithromycin as Adjunctive Therapy for Uncomplicated Severe Acute Malnutrition:

Conditions
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Uncomplicated Severe Acute Malnutrition

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Amoxicillin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>children in this arm will receive one dose of azithromycin | Drug: Azithromycin<br>* 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.<br>* Other names: Zithromax;|
| Active Comparator: Amoxicillin<br>Children in this arm will receive a 7 day course of amoxicillin (standard of care) | Drug: Amoxicillin<br>* 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.<br>|

What is the study measuring?
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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 |