Azithromycin for Severe Acute Malnutrition in CMAM, Nigeria

Study Overview
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Brief Summary
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This randomized controlled trial is designed to determine the effect of administration of azithromycin compared to amoxicillin as part of the treatment of uncomplicated severe acute malnutrition (SAM) in children aged 6-59 months on weight gain and nutritional recovery. The investigators will randomize children presenting to Taimaka-run nutritional programs at health centers in Gombe State, Nigeria to a single dose of oral azithromycin or a short course of oral amoxicillin upon admission into the program. Apart from the administration of antibiotics, all children will receive standard outpatient treatment for uncomplicated SAM as specified in the guidelines of the government of Nigeria, which includes therapeutic feeding with ready-to-use therapeutic food (RUTF). Enrolled children will be followed weekly at each routine clinic follow-up visit up until nutritional recovery. All enrolled children will return for a final study visit at 8 weeks following enrollment. Anthropometric and vital status data will be collected at each follow-up visit. Weight gain and nutritional recovery over the 8-week study period will be compared by arm as a primary outcome and at 12 weeks as a secondary outcome.

Official Title
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Azithromycin for Severe Acute Malnutrition in CMAM, Nigeria

Conditions
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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 (all must be met): Age 6-59 months Weight-for-height z-score (WHZ) < -3 SD or mid-upper arm circumference (MUAC) < 115 mm No nutritional or nutritional edema Grade I and II Primary residence within catchment area of enrollment site Available for full 8-week study Has not been admitted to a nutritional program for the treatment of severe acute malnutrition (SAM) in the 2 preceding weeks No antibiotic use in past 7 days No clinical complications requiring antibiotic treatment No clinical complications requiring inpatient treatment 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, sickle cell disease, etc) No allergy to macrolides/azalides Sufficient appetite according to a feeding test with ready-to-use therapeutic food (RUTF) Appropriate written informed consent from at least one parent or guardian Exclusion criteria (any excludes): Age < 6 months or > 59 months WHZ ≥ -3 SD or MUAC ≥ 115 mm Primary residence outside catchment area of enrollment site Not available for full 8-week study Presence of nutritional edema Grade III Admission to a nutritional program for the treatment of SAM in the 2 preceding weeks Antibiotic use in past 7 days Clinical complications requiring antibiotic treatment 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 amoxicillin. | Drug: Azithromycin<br>* Children enrolled in the trial and randomized to receive azithromycin will receive a single dose of azithromycin at 20 mg/kg up to the maximum adult dose of 1g. Oral azithromycin will be administered at the time of enrollment. Enrolled children will also receive RUTF.<br>|
| Active Comparator: Amoxicillin<br>Children in this arm will receive a 5-day course of amoxicillin (standard care). | Drug: Amoxicillin<br>* Children enrolled in the trial and randomized to receive amoxicillin will receive a 5-day course of amoxicillin to be given in twice-daily doses of 15 mg/kg per the Nigeria guidelines for severe acute malnutrition. The first dose will be administered at the time of enrollment, and the remaining doses 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 at 8 weeks | Weight will be measured at baseline and weekly follow ups, and weight gain will be calculated at 8 weeks in g/kg/day | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional Recovery at 8 weeks | Nutritional recovery will be defined as a child having WHZ ≥ -2 on two consecutive visits and no acute complication or edema for the past 7 days AND / OR MUAC of ≥ 125mm on 2 consecutive visits and no acute complication or edema for the past 7 days. Children will be considered recovered or not recovered using these criteria Anthropomorphic outcomes are defined according to the World Health Organization's 2006 Child Growth Standards A z-score of 0 represents the population median. The z-score will be positive if the data value lies above the mean, and it will be negative if the value lies below the median. A WHZ < -2 standard distributions below the median is defined as moderately wasted, while a WHZ < -3 standard distributions below the median is defined as severely wasted. | 8 weeks |