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

Primary Purpose

Uncomplicated Severe Acute Malnutrition

Status
Completed
Phase
Phase 3
Locations
Burkina Faso
Study Type
Interventional
Intervention
Azithromycin
Amoxicillin
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uncomplicated Severe Acute Malnutrition

Eligibility Criteria

6 Months - 59 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre de Recherche en santé de nouna

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Azithromycin

Amoxicillin

Arm Description

children in this arm will receive one dose of azithromycin

Children in this arm will receive a 7 day course of amoxicillin (standard of care)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
Malaria
Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to determine malaria infection status.
Mortality
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)
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)
Mid-upper arm circumference will be measured at all follow-up time points
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.
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
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.

Full Information

First Posted
June 14, 2018
Last Updated
August 10, 2022
Sponsor
University of California, San Francisco
Collaborators
Centre de Recherche en Sante de Nouna, Burkina Faso, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT03568643
Brief Title
Azithromycin for Uncomplicated Severe Acute Malnutrition in Burkina Faso (Pilot)
Acronym
SAM
Official Title
Azithromycin as Adjunctive Therapy for Uncomplicated Severe Acute Malnutrition:
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
June 3, 2020 (Actual)
Primary Completion Date
December 25, 2020 (Actual)
Study Completion Date
December 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Centre de Recherche en Sante de Nouna, Burkina Faso, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uncomplicated Severe Acute Malnutrition

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
301 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Azithromycin
Arm Type
Experimental
Arm Description
children in this arm will receive one dose of azithromycin
Arm Title
Amoxicillin
Arm Type
Active Comparator
Arm Description
Children in this arm will receive a 7 day course of amoxicillin (standard of care)
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Weight Gain
Description
Weight will be measured at all follow-up time points and weight gain will be calculated at 8 weeks
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Nutritional Recovery - Primary Definition
Description
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
Time Frame
8 weeks
Title
Nutritional Recovery - Secondary Definition
Description
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.
Time Frame
8 weeks
Title
Malaria
Description
Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to determine malaria infection status.
Time Frame
8 weeks
Title
Mortality
Description
Vital status will be assessed at all follow-up time points and mortality will be defined as death during the study period.
Time Frame
8 weeks
Title
Length/Height-for-age Z-score (LAZ/HAZ)
Description
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
Time Frame
8 weeks
Title
Mid-Upper Arm Circumference (MUAC)
Description
Mid-upper arm circumference will be measured at all follow-up time points
Time Frame
8 weeks
Title
Weight-for-Age Z-scores (WAZ)
Description
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.
Time Frame
8 weeks
Title
Weight-for-Height Z-score (WHZ)
Description
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
Time Frame
8 weeks
Title
Intestinal Microbiome
Description
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.
Time Frame
Baseline, 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine E Oldenburg, ScD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de Recherche en santé de nouna
City
Nouna
State/Province
Boucle Du Mouhoun
Country
Burkina Faso

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35895362
Citation
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.
Results Reference
derived
PubMed Identifier
34583344
Citation
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.
Results Reference
derived
PubMed Identifier
33879263
Citation
O'Brien KS, Sie 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.
Results Reference
derived

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

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