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

Phase 3

Completed

Conditions: Uncomplicated Severe Acute Malnutrition

Interventions: Drug: Azithromycin
Drug: Amoxicillin

Registration Number: NCT03568643

Lead Sponsor: University of California, San Francisco

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 301

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azithromycin	Azithromycin	children in this arm will receive one dose of azithromycin
Amoxicillin	Amoxicillin	Children in this arm will receive a 7 day course of amoxicillin (standard of care)

Primary Outcome Measures

Name	Time	Method
Weight Gain	8 weeks	Weight will be measured at all follow-up time points and weight gain will be calculated at 8 weeks

Secondary Outcome Measures

Name	Time	Method
Nutritional Recovery - Primary Definition	8 weeks	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
Nutritional Recovery - Secondary Definition	8 weeks	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.
Malaria	8 weeks	Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to determine malaria infection status.
Mortality	8 weeks	Vital status will be assessed at all follow-up time points and mortality will be defined as death during the study period.
Length/Height-for-age Z-score (LAZ/HAZ)	8 weeks	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
Mid-Upper Arm Circumference (MUAC)	8 weeks	Mid-upper arm circumference will be measured at all follow-up time points
Weight-for-Age Z-scores (WAZ)	8 weeks	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.
Weight-for-Height Z-score (WHZ)	8 weeks	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
Intestinal Microbiome	Baseline, 8 weeks	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.