Azithromycin for Severe Acute Malnutrition in CMAM, Nigeria

• ClinicalTrials.gov Identifier: NCT05473234
• Recruitment Status: Recruiting
• First Posted: July 25, 2022
• Last Update Posted: February 3, 2023
• Sponsor: University of California, San Francisco
• Collaborator: The Taimaka Project
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Severe Acute Malnutrition	Drug: Azithromycin; Drug: Amoxicillin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Azithromycin for Severe Acute Malnutrition in CMAM, Nigeria
• Actual Study Start Date: October 6, 2022
• Estimated Primary Completion Date: November 1, 2024
• Estimated Study Completion Date: November 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azithromycin; Children in this arm will receive one dose of amoxicillin.	Drug: Azithromycin; 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.
Active Comparator: Amoxicillin; Children in this arm will receive a 5-day course of amoxicillin (standard care).	Drug: Amoxicillin; 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.

Outcome Measures

Primary Outcome Measures :

1. Weight Gain at 8 weeks [ Time Frame: 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

Secondary Outcome Measures :

1. Nutritional Recovery at 8 weeks [ Time Frame: 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.

Other Outcome Measures:

1. Weight Gain over 12 weeks [ Time Frame: 12 weeks ]
   Weight will be measured at baseline and weekly follow up visits for 8 weeks, and at 12 weeks after admission to the program. Weight gain will be defined as grams per kilogram per day (g/kg/day).
2. Time to recovery [ Time Frame: 12 weeks ]
   Time from enrollment to nutritional recovery will be calculated in days by subtracting the date of enrollment from the date of nutritional recovery.
3. Nonresponse at 8 weeks [ Time Frame: 8 weeks ]
   Number of children with nonresponse will be documented if a child does not meet the criteria for nutritional recovery at 8 weeks after enrollment.
4. Transfer to inpatient care [ Time Frame: 12 weeks ]
   The occurrence, date, and reason for transfer from outpatient to inpatient treatment will be recorded.
5. Mortality by 8 weeks [ Time Frame: 8 weeks ]
   Vital status will be assessed at baseline and at weekly follow up visits for 8 weeks, and mortality will be defined as death during the study period. Date of death will be recorded.
6. Mortality by 12 weeks [ Time Frame: 12 weeks ]
   Vital status will be assessed at baseline, weekly follow up visits for 8 weeks, and at 12 weeks, and mortality will be defined as death during the study period. Date of death will be recorded.
7. Clinical signs of infection [ Time Frame: 12 weeks ]
   Number of participants with clinical sign of infection will be recorded At baseline, weekly follow up visits for 8 weeks, and at the 12-week follow up visit, including care-giver reported experience of fever, diarrhea, vomiting, and respiratory infection/cough and clinical diagnoses made at by site personnel
8. Height-for-age z-score (HAZ) [ Time Frame: 12 weeks ]

   Height or length will be measured monthly (baseline and the 4-, 8-, and 12-week follow up visits) and height-for-age z-scores will be calculated.

   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 HAZ < -2 standard distributions below the median is defined as stunted, while a HAZ < -3 standard distributions below the median is defined as severely stunted.

9. Mid-upper arm circumference (MUAC) [ Time Frame: 12 weeks ]
   Mid-upper arm circumference (centimeters) will be measured at all follow-up time points (baseline, weekly follow up visits for 8 weeks, and at the 12-week follow up visit).
10. Weight-for-age z-score (WAZ) [ Time Frame: 12 weeks ]

    Weight will be measured at all follow-up time points (baseline, weekly follow up visits for 8 weeks, and at the 12-week follow up visit) and weight-for-age z-scores will be calculated.

    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 WAZ < -2 standard distributions below the median is defined as underweight, while a WAZ < -3 standard distributions below the median is defined as severely underweight.

11. Weight-for-height z-score (WHZ) [ Time Frame: 12 weeks ]

    Weight and height, assessed at all follow-up time points (baseline, weekly follow up visits for 8 weeks, and at the 12-week follow up visit), will be used to calculate weight-for-height z-scores.

    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 WAZ < -3 standard distributions below the median is defined as severely wasted.

12. Malaria [ Time Frame: 8 weeks ]
    Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to determine malaria infection status. Positivity rate will be compared between arms

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Catherine E Oldenburg, ScD; 4155028843; catherine.oldenburg@ucsf.edu

Contact: Hadley R Burroughs, MSPH; 4155022521; Hadley.burroughs@ucsf.edu

Locations

Nigeria

The Tamaika Project; Recruiting

Gombe, Gombe State, Nigeria, 760252

Contact: Abubakar Umar, MBBS 2348061307990 abubakar@taimaka.org

Sponsors and Collaborators

University of California, San Francisco

The Taimaka Project

Investigators

• Principal Investigator: Kieran S O'Brien, PhD; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT05473234
• Other Study ID Numbers: 22-36912
• First Posted: July 25, 2022
• Last Update Posted: February 3, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Malnutrition; Severe Acute Malnutrition; Nutrition Disorders; Amoxicillin; Azithromycin; Anti-Bacterial Agents; Anti-Infective Agents