Clinical trial NCT03568643
Conditions: Uncomplicated Severe Acute Malnutrition
Sponsor: University of California, San Francisco
Start date: 2020-06-03; Completion date: 2020-12-25
Enrollment: 301 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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:

Arms: arm 1: children in this arm will receive one dose of azithromycin arm 2: Children in this arm will receive a 7 day course of amoxicillin (standard of care)
Interventions: intervention 1: Azithromycin intervention 2: Amoxicillin
Intervention descriptions: intervention 1: 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 2: 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.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Azithromycin as Adjunctive Therapy for Uncomplicated Severe Acute Malnutrition:  
An individual-randomized pilot trial of the effect of a single dose of oral azithromycin on 
weight gain in children with uncomplicated severe acute malnutrition in Burkina Faso  
 
Manual of Operations and Procedures 
 
 
Centre de Recherche en Santé de Nouna 
 
The Francis I. Proctor Foundation, Global Health Sciences 
University of California, San Francisco 
 
Ali Sié, MD, PhD 
Kieran O’Brien, MPH 
Travis Porco, PhD MPH 
Benjamin Arnold, PhD MPH 
Elodie Lebas, RN 
Catherine Oldenburg, ScD MPH 
 
 
Trial registration: clinicaltrials.gov (NCT03568643) 
 
Date document : March 1 2021


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
2 
TABLE OF CONTENTS 
 
 
ABBREVIATIONS ........................................................................................................................ 4 
1. 
INTRODUCTION .................................................................................................................. 5 
2. 
STUDY DESIGN.................................................................................................................... 7 
2.1. 
Study Setting ................................................................................................................... 7 
2.2. 
Recruitment and Eligibility Criteria ................................................................................ 7 
2.3. 
Randomization and Masking .......................................................................................... 8 
2.4. 
Interventions ................................................................................................................... 9 
2.5. 
Outcomes ........................................................................................................................ 9 
2.6. 
Participant Timeline ...................................................................................................... 11 
2.7. 
Study Team, Roles, Responsibilities ............................................................................ 12 
3. 
PROCEDURES .................................................................................................................... 13 
3.1. 
Training ......................................................................................................................... 13 
3.2. 
Anthropometry .............................................................................................................. 13 
3.3. 
Malaria Rapid Diagnostic Test ..................................................................................... 21 
3.4. 
Rectal swab collection .................................................................................................. 22 
Procedure .............................................................................................................................. 22 
Materials for Rectal Swab Collection ................................................................................... 23 
3.5. 
Vital Status .................................................................................................................... 24 
3.6. 
Clinical examination ..................................................................................................... 24 
4. 
STUDY MEDICATION ....................................................................................................... 25 
5. 
ADVERSE EVENTS ............................................................................................................ 26 
6. 
DATA COLLECTION, MANAGEMENT, AND SECURITY ........................................... 27 
6.1. 
Data Collection ............................................................................................................. 27 
6.2. 
Data Management and Security .................................................................................... 27 
6.3. 
Data Quality and Monitoring ........................................................................................ 27 
7. 
PROTECTION OF HUMAN SUBJECTS ........................................................................... 28 
7.1. 
Institutional Review Board Approval ........................................................................... 28 
7.2. 
Informed Consent .......................................................................................................... 28 
8. 
DATA AND SAFETY MONITORING COMMITTEE ...................................................... 29 
9. 
STATISTICAL METHODS ................................................................................................. 30 
9.1. 
Sample Size and Power ................................................................................................. 30 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
3 
9.2. 
Statistical Analysis ........................................................................................................ 30 
REFERENCES ............................................................................................................................. 32 
REVISIONS HISTORY ............................................................................................................... 33 
APPENDIX ................................................................................................................................... 34 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
4 
ABBREVIATIONS 
 
CHW: Community Health Worker 
CSPS: Centre de Santé et de Promotion Sociale 
DSMC: Data and Safety Monitoring Committee 
HAZ: height-for-age z-score 
IRB: Institutional Review Board 
MUAC: mid-upper arm circumference  
RDT: rapid diagnostic test 
RUTF: ready-to-use therapeutic food 
SAM: severe acute malnutrition 
SD: standard deviation 
SES: socio-economic status 
UCSF: University of California San Francisco  
WAZ: weight-for-age z-score 
WHO: World Health Organization 
WHZ: weight-for-height z-score 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
5 
1. INTRODUCTION 
 
1.1 
Background and Rationale 
 
Severe acute malnutrition (SAM) affects nearly 19 million children under the age of 5 
annually.1 Current World Health Organization (WHO) guidelines for treatment of SAM include 
outpatient treatment with ready-to-use therapeutic food (RUTF). Children with SAM often bear a 
large burden of infectious disease, have 9 times the risk of all-cause mortality compared to their 
well-nourished peers, and face a stronger risk of infectious mortality.2,3 Because malnutrition 
can suppress the immune system, children with SAM and co-existing infection are often 
asymptomatic. As a result, the WHO has recommended that the routine treatment of children 
with SAM include a broad-spectrum antibiotic. However, the evidence base for this 
recommendation is minimal. Two studies of amoxicillin as adjunctive therapy for SAM found 
mixed results.4,5  In Malawi, routine amoxicillin led to increased nutritional recovery and 
decreased mortality.4 In Niger, there was no effect of routine amoxicillin on either nutritional 
recovery or mortality.5 Importantly, a majority of the children included in the Malawi study had 
kwashiorkor, whereas children with kwashiorkor were excluded in Niger. A pooled analysis of 
the two studies found no benefit of amoxicillin for recovery.6 A third study of daily co-trimoxazole 
for complicated SAM additionally found no benefit for nutritional recovery or mortality.7 The role 
of antibiotics for mortality and nutritional recovery among children with uncomplicated severe 
acute malnutrition remains unclear. 
 
A recent cluster-randomized trial demonstrated that mass azithromycin distribution 
reduces all-cause mortality at the community level.8 In Niger, Tanzania, and Malawi, 
mortality was reduced by nearly 14% in communities randomized to biannual mass single-dose 
azithromycin distribution to children 1-59 months in the MORDOR trial (Macrolides Oraux pour 
Réduire les Décès avec un Oeil sur la Résistance). The largest effects were seen in Niger, with 
nearly 1 in 5 deaths averted, and in children less than 6 months of age, with approximately 25% 
reduction in mortality.  
 
Azithromycin as adjunctive therapy may offer several advantages over amoxicillin or co-
trimoxazole. First, a single dose of azithromycin has a long half-life, and thus dosing could 
occur during outpatient follow-up visits and would not rely on caregiver dosing. Second, 
amoxicillin and co-trimoxazole are much more commonly used for routine treatment in many 
regions of sub-Saharan Africa than macrolides, and baseline resistance to these antibiotic 
classes tend to be much higher.9 Adjunctive therapy with azithromycin may be preferable, given 
overall reduced exposure compared to other classes.10 Third, evidence from the MORDOR 
study in Niger indicated a substantial reduction in mortality with the use of a single dose of 
azithromycin in children without established infection. Given that children with uncomplicated 
SAM by definition do not have an established infection, the rationale for antibiotic use may be 
similar for that among children in the general population who are receiving presumptive 
treatment. As children with malnutrition are at particularly high risk of mortality, this subgroup of 
the population may stand to see greater benefits from a similar antibiotic regimen that has been 
shown to be efficacious in the general population.  
 
 
 
 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
6 
1.2 
Design Overview  
 
We propose a randomized controlled trial to examine the effect of the adjunctive administration 
of azithromycin compared to amoxicillin in the treatment of children aged 6-59 months with 
uncomplicated SAM. We will randomize children presenting to nutritional programs in Burkina 
Faso to a single dose of oral azithromycin or a short course of oral amoxicillin upon admission 
into the program and follow them at each weekly clinic follow-up visit up to 8 weeks following 
admission. All enrolled children with receive non-antibiotic routine care for uncomplicated SAM 
in Burkina Faso, which includes RUTF. Anthropometric and vital status data will be collected 
during follow-up. Weight gain and nutritional recovery over the 8-week study period will be 
compared by arm. 
 
1.3 
Objectives 
 
SPECIFIC AIM 1: Determine the effect of azithromycin on weight gain among children 
with uncomplicated SAM. We hypothesize that children randomized to receive azithromycin 
will experience greater weight gain over an 8-week period compared to those receiving 
amoxicillin.    
 
 
SPECIFIC AIM 2: Determine the effect of azithromycin on nutritional recovery in children 
with uncomplicated SAM. We hypothesize that children randomized to receive azithromycin 
will have increased nutritional recovery 8 weeks after admission to the nutritional program 
compared to children receiving amoxicillin. 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
7 
 
2. STUDY DESIGN 
 
The proposed study is a pilot trial conducted in preparation for a future, larger trial. This 
randomized controlled trial is designed to determine the effect of administration of azithromycin 
compared to amoxicillin as part of the treatment of uncomplicated SAM in children aged 6-59 
months on weight gain and nutritional recovery. We will randomize children presenting to 
nutritional programs at health centers in Burkina Faso 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 Burkina Faso, 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. 
 
2.1. 
Study Setting 
 
The trial will be conducted at Centre de Santé et de Promotion Sociale (CSPS) that run 
nutritional programs for children presenting with SAM. CSPSs are government-run integrated 
health centers linked to and overseen by district hospitals. 
 
2.2. 
Recruitment and Eligibility Criteria 
 
Recruitment 
 
Community health workers (CHWs) will be trained by the study team to actively seek cases of 
SAM in the study area and refer them to a study CSPS. CHWs will screen for SAM using tape to 
measure mid-upper arm circumference (MUAC) and will refer children with MUAC < 115 mm to 
a study CSPS. 
 
Each participating enrollment site will be assigned at least one dedicated study team member 
who will enter data and conduct outcome assessments. The study team member will be either 
an existing member of enrollment site staff who will be trained for the study or an external study 
team member who will be placed at the site for the duration of the study. 
 
This study team member will review the site logbook and/or medical records every day to 
identify children who are potentially eligible for participation, including both children referred by 
CHWs and children presenting independently. The team member will approach the parent or 
guardian of potentially eligible children to confirm eligibility according to the criteria listed below. 
 
Eligibility criteria for enrollment sites 
 
For inclusion in the pilot trial, sites must meet the following criteria: 
1. More than 200 cases of severe acute malnutrition seen in 2017 
2. Willing to participate in the trial 
3. Participation approved by the district 
 
Eligibility criteria for individuals 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
8 
Eligible individuals are children aged 6-59 months with SAM who present to an eligible 
enrollment site during the study period and meet all of the following 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 edema 
• 
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 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, 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 
• 
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 
 
2.3. 
Randomization and Masking 
 
Children meeting inclusion criteria will be enrolled by local trained study personnel. At 
enrollment, children will be assigned a study identification number using the next unassigned 
number on a list identification numbers assigned to the site. Enrolled children will then undergo 
a baseline assessment. The baseline assessment includes data collection on demographics 
and socioeconomic status, anthropometric assessments, and a malaria rapid diagnostic test 
(RDT; see Figure 1 and Section 3 for details). After completion of the baseline assessment, 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
9 
children will be randomized to receive either a single dose of directly observed oral azithromycin 
or a 7-day course of oral amoxicllin. 
 
The randomization sequence will be generated by the UCSF investigators using R (R 
Foundation for Statistical Programming, Vienna, Austria). Children will be randomized in a 1:1 
fashion to a single dose of azithromycin or a short course of oral amoxicillin. The randomization 
sequence will be linked to the study identification numbers. Randomized study arm assignments 
will be placed in sealed, opaque envelopes labeled with study identification numbers. When a 
child has been enrolled and has completed the baseline assessments, a CSPS nurse trained for 
the study will open the envelope to determine the allocation, and will administer study 
medication indicated as described in Sections 2.4 and 4.  
 
To keep the allocation concealed, only the study nurse administering treatment will have access 
to the envelopes with the randomization allocations. The study nurse will open the envelope and 
administer treatment in a private room without the outcome assessor present. For each enrolled 
child, the study nurse will record whether or not azithromycin was administered on a paper form 
kept in a locked cabinet not accessible by the outcome assessor. 
 
Given the nature of the intervention, participants and study personnel administering treatment 
will not be masked to treatment assignment. Outcome assessors will be masked to treatment 
assignment; this will be accomplished by assigning one CSPS nurse to administer treatment 
and a separate masked study team member to perform outcome assessments, including 
anthropometry, malaria RDT, and vital status updates.  
 
2.4. 
Interventions 
 
Children will be randomized to receive a single, directly observed dose of oral azithromycin or a 
short course of oral amoxicillin, which will be administered at the time of enrollment (see Section 
4 for study medication details). Except for antibiotics, all children will receive standard outpatient 
treatment for uncomplicated SAM per the guidelines of the government of Burkina Faso, which 
includes RUTF (170 kcal per kilogram per day; Plumpy’Nut, Nutriset). In Burkina Faso, standard 
treatment includes weekly follow-up visits to monitor anthropometric indicators. Enrolled children 
will be followed weekly at each routine clinic follow-up visit until nutritional recovery and again at 
8 weeks following admission.  
Standard of care of the outpatient management of SAM in Burkina Faso includes a short course 
of oral amoxicillin. Children enrolled in this study will not receive oral amoxicillin, regardless of 
randomization assignment. 
 
2.5. 
Outcomes 
 
Primary Outcome 
• 
Weight gain over 8 weeks (Specific Aim 1). Weight will be measured at all follow-up 
time points and weight gain will be defined as grams per kilogram per day (g/kg/day). 
 
Secondary Outcomes 
• 
Nutritional recovery by 8 weeks (Specific Aim 2). 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 OR MUAC of ≥ 125mm on 2 consecutive visits and no acute 
complication or edema for the past 7 days. The criteria chosen to define the recovery will 
be the same one we used to admit the child into the program. 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
10 
• 
Time to recovery. Time from enrollment to nutritional recovery (defined above) will be 
calculated in days by subtracting the date of enrollment from the date of nutritional 
recovery. 
• 
Nonresponse at 8 weeks. Nonresponse will be documented if a child does not meet the 
criteria for nutritional recovery at 8 weeks. 
• 
Transfer to inpatient care. The occurrence, date, and reason for transfer from 
outpatient to inpatient treatment will be recorded. 
• 
Mortality by 8 weeks. Vital status will be assessed at all follow-up time points and 
mortality will be defined as death during the study period. Date of death will be recorded. 
• 
Clinical signs of infection. At all follow-up time points, clinical signs of infection will be 
recorded, including care-giver reported experience of fever, diarrhea, vomiting, and 
respiratory infection/cough and clinical diagnoses made at by site personnel 
• 
Adverse events. Adverse events will be reported at all follow-up time points (defined in 
Section 5). 
• 
HAZ. Height or length will be measured at all follow-up time points and height-for-age z-
scores will be calculated. 
• 
MUAC. Mid-upper arm circumference will be measured at all follow-up time points. 
• 
WAZ. Weight will be measured at all follow-up time points and weight-for-age z-scores 
will be calculated. 
• 
WHZ. Weight and height, assessed at all follow-up time points, will be used to calculate 
weight-for-height z-scores. 
• 
Malaria. Rapid diagnostic tests for malaria will be conducted at baseline and week 8 to 
determine malaria infection status. 
• 
Intestinal microbiome: Rectal swabs will be collected in a random subset of children at 
baseline and at week 8.  
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
11 
2.6. 
Participant Timeline 
 
Figure 1. Participant Timeline and Flow 
 
Children Admitted to Nutritional Program 
 
 
Eligibility Criteria: 
• 
Age 6-59 months 
• 
WHZ <-3 SD or MUAC <115 mm  
• 
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 SAM in the 3 
preceding months 
• 
No edema 
• 
No antibiotic use in past 7 days 
• 
No clinical complications requiring antibiotic treatment 
• 
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 
 
 
 
Baseline assessment: 
• 
Baseline questionnaire (feeding practices, household survey, maternal survey) 
• 
Anthropometry (height, weight, MUAC) 
• 
Malaria (RDT) 
• 
Rectal swab (random subset of children) 
• 
Hemoglobin 
 
 
 
Randomized 
 
 
 
 
Randomized to single dose azithromycin 
 
Randomized to a short course of oral 
amoxicillin 
 
 
 
Weeks 1-7: 
• 
Anthropometry (height, weight, MUAC) 
• 
Adverse Events 
• 
Vital Status 
• 
Clinical examination outcomes (diagnoses, treatments) 
 
Week 8: 
• 
Anthropometry (height, weight, MUAC)  
• 
Adverse events 
• 
Vital Status 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
12 
• 
Malaria (RDT) 
• 
Rectal swab (random subset of children) 
• 
Hemoglobin 
• 
Clinical examination outcomes (diagnoses, treatments) 
 
 
 
2.7. 
Study Team, Roles, Responsibilities 
• 
Investigators (UCSF). The UCSF investigators will be responsible for the overall study 
design and implementation, data management and monitoring, data analysis, and 
dissemination of results in collaboration with UCSF investigators. The UCSF 
investigators will design and implement trainings for study procedures and maintain 
weekly communication with local Burkina Faso study staff. 
• 
Investigators (CRSN). The CRSN investigators will be responsible for overall study 
design, implementation, data management and monitoring, data analysis, and 
dissemination of results in collaboration with UCSF investigators. The Burkina Faso 
investigators will oversee all local study activities, including training and regular 
supervision and monitoring of local study staff. 
• 
Medical Monitor. The Medical Monitor will provide clinical oversight for the enrolled 
children. Study Team Members will report serious adverse events to the Medical Monitor 
within 24 hours of occurrence, and the Medical Monitor will determine whether or not the 
event is likely to be related to the study drug. In addition, the Medical Monitor will provide 
clinical guidance for the adverse event as needed. The Medical Monitor will participate 
on the Data and Safety Monitoring Committee. 
• 
Data and Safety Monitoring Committee. The Data and Safety Monitoring Committee 
will provide independent oversight of data quality and patient safety during the course of 
the trial. See Section 8 for details. 
• 
Study Team Members (CRSN). Study Team Members at CRSN will be responsible for 
implementation of all study procedures as described in Section 3, including recruitment, 
consent, enrollment and randomization, drug administration, and collection of all study 
data, including anthropometric and malaria assessments. 
o CSPS Nurse. A nurse at each CSPS will be trained to determine the 
randomization allocation of enrolled children by opening the envelopes and to 
administer azithromycin if indicated. 
o Outcome Assessor. One outcome assessor for each site will be trained to 
manage consent, enrollment, and collection of all study data, including outcome 
assessments. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
13 
3. PROCEDURES 
 
3.1. 
Training 
 
All study personnel participating in study procedures (including enrollment and baseline 
assessment, randomization, drug administration, outcome assessments, and data collection) 
will participate in a 2-day initial training. Training will include a mix of lecture and practice. 
Participants must achieve a score of >80% on the training quiz in order to participate in the 
study and demonstrate agreement with a gold standard grader for all anthropometric 
assessments. Study personnel will be overseen by study investigators during the first week of 
enrollment, and refresher training will be conducted once a month during the course of the 
study. 
 
3.2. 
Anthropometry 
 
Anthropometric assessments (height or length, weight, and MUAC) will be recorded by study 
personnel at baseline, weekly until recovery, and at week 8. 
 
Supplies 
• 
Mobile data collection device & accessories 
• 
ShorrBoard 
• 
Seca scale  
• 
MUAC strips  
• 
Chucks and alcohol swabs 
• 
Pens and sharpie markers 
• 
Trash bags 
• 
Extra set of AA batteries (6) 
 
Anthropometry Team 
Two study team members will conduct anthropometry: 1) examiner and 2) recorder. The 
examiner will conduct the anthropometric assessments, and the recorder will enter data into the 
mobile application. 
 
Measuring Length and Height 
A lightweight measuring board will be used to measure the participant’s height to the nearest 
0.1 cm. Height and length will be assessed with a ShorrBoard. Depending on a child’s age and 
ability to stand, measure the child’s length or height.   
• 
Length: If a child is less than 2 years old, or cannot stand alone, measure recumbent 
length.  The recorder will select Length in the application to indicate that length was 
measured. A child’s length is measured lying down (recumbent).   
• 
Height: If a child is able to stand, measure standing height.  The recorder will select 
Height in the application to indicate that height was measured. Height is measured 
standing upright. 
 
If the child has braids or hair ornaments that will interfere with length/height measurements, 
remove them if possible.  Check that any sandals, shoes, or socks have also been removed.  
Whether measuring length or height, the mother/guardian is needed to help with measurements 
and to soothe and comfort the child.  Explain to the mother the reasons for the measurements, 
and describe the steps in the procedure. Answer any questions she might have. Show her and 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
14 
tell her how she can help you. Explain that it is important to keep the child still and calm to 
obtain the best measurement.  
 
Measure Length  
1. Cover the length board with a chuck for hygiene and for the baby’s comfort. 
2. We usually have the assistant anthropometrist hold the baby's head and the lead anthropometrist 
manage the legs and feet. The mother stands to the side and focuses primarily on soothing the 
baby. The lead anthropometrist calls out the measurement and the assistant repeats it and then 
records it on the tablet.  
3. Ask the mother to stand nearby and focus on soothing the baby. 
4. The assistant anthropometrist will place the baby on the length board on his/her back 
with his/her head fixed against the headboard, compressing the hair and will hold the 
baby’s head in place while the measurement is taken. The assistant should move quickly 
and surely without distressing the baby. 
5. The assistant anthropometrist will quickly position the head so that an imaginary vertical 
line from the ear canal to the lower border of the eye socket is perpendicular to the 
board.  (The child’s eyes should be looking straight up.)   
6. Speed is important.  The lead anthropometrist will manage the baby’s legs and feet. 
Standing on the side of the length board where you can see the measuring tape and 
move the footboard:  
a. Check that the child lies straight along the board and does not change position.   
b. Shoulders should touch the board, and the spine should not be arched. Ask the 
mother to inform you if the child arches the back or moves out of position.   
c. Hold down the child’s legs with the one hand and move the footboard with the 
other. Apply gentle pressure to the knees to straighten the legs as far as they can 
go without causing injury or distress.  Note: it is not possible to straighten the 
knees of newborns to the same degree as older children.  Their knees are 
fragile and could be easily injured, so apply only gentle pressure.   
ShorrBoard Set-Up 
1) Remove ShorrBoard from bag. 
2) Stand the ShorrBoard upright.  You can step on the base of the board to keep it 
stable. 
3) As you face the board, turn the non-removable bolt counterclockwise to release the 
extension piece.  Note: the bolt remains attached to the back of the extension piece – 
do NOT remove it. 
4) Slide the extension piece into the top end of the main board and fasten the clasp on 
the back of the board.  Make sure the clasp is fastened properly.   
5) The auto-lock sliding head/footpiece is stored in the base of the main board and can 
be moved up and down the length of the measuring board. It should stay in place on 
its own wherever you position it.   
6) The measuring board must be placed against a firm surface for standing height (e.g. 
wall, table, tree, against a vehicle, etc.). Make sure the board is stable. If necessary, 
place items such as small rocks underneath the height board to stabilize it during the 
measurement.  
7) Clean the equipment with alcohol swabs at the beginning of each day, and clean with 
alcohol swabs between each participant. 
 
Note: when you set up the board each day, examine each of the pieces to check for damage. 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
15 
d. If a child is extremely agitated and both legs cannot be held in position, measure 
with one leg in position.  
e. While holding the knees, pull the footboard against the child’s feet.  Many babies 
will point their toes, but the lead anthropometrist should ensure the feet are 
perpendicular to the back of the board as much as possible. 
7. Upon reading the measurement, the examiner will clearly call out the number to 
the recorder.  Record the child’s length in centimeters to the last completed 0.1 cm.  
(1.0 mm).   
8. Keeping the child in place, release the sliding footboard, and prepare to repeat the 
measurement.  Re-position the child for a second and third measurement.  
 
 
 
 
 
 
 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
16 
Measure Standing Height 
1. Ensure that the height board is on level ground.   
2. Working with the mother, and kneeling in order to be at the level of the child: 
a. Help the child stand on the baseboard with the weight of the child evenly 
distributed on both feet.  The heels of the feet are placed together with both heels 
touching the base of the vertical board.  Place the feet pointed slightly outward at 
a 60 degree angle. 
b. The back of the head, shoulder blades, buttocks, calves, and heels should all 
touch the vertical board.  Arms should hang freely by the sides of the body with 
the palms facing the thighs.  Note: Standing with all body parts touching the 
board may be difficult for some children, in which case, help the child to 
stand on the board with one or more contact points touching the board. 
c. Ask the mother to hold the child’s knees and ankles to help keep the legs straight 
and feet flat, with heels and calves touching the vertical board.  Ask her to focus 
the child’s attention, soothe the child as needed, and inform you if the child 
moves out of position.  
d. Position the child’s head so that a horizontal line from the ear canal to the lower 
border of the eye socket runs parallel to the baseboard.   
e. Ask the child to inhale deeply and to stand fully erect without altering the position 
of the heels.  If necessary, push gently on the belly to help the child stand to full 
height.  
f. Still keeping the head in position, use your other hand to pull down the 
headboard to rest firmly on top of the head and compress the hair. 
3. Upon reading the measurement, the examiner will clearly call out the number to 
the recorder.  Record the child’s height in centimeters to the last completed 0.1 cm (1.0 
mm). 
4. Keeping the child in place, release the sliding headboard, and prepare to repeat the 
measurement.  Re-position the child for a second and third measurement.    


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
17 
 
 
 
 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
18 
 
Measuring Weight 
The SECA 874 scale will be used to weigh infants and children to the nearest 0.1 kg. Infants 
and young children can also be weighed simultaneously with their parent or guardian by the 
unique “mother-baby” function (parent or guardian is weighed and then the infant or child is 
weighed while held by the parent). 
 
Explain to the mother that we want to weigh her child to see how he or she is growing.  If she 
has a baby or a child who is unable to stand, she will hold the child on the scale.  If the child is 2 
years or older/can stand alone, the child will be weighed alone.   
Children should be wearing only light clothing, no shoes or sandals, no hair ornaments, and no 
jewelry. Explain that the child needs to remove outer clothing and shoes/sandals in order to 
obtain an accurate weight.  If the baby is wearing a diaper, the diaper should be removed.  If 
any heavy clothes remain on the child, make a note in the Notes section. 
 
 
Turn the power on the scale when you are ready to begin weighing.  
1. If the child is unable to stand on the scale, you will use the 2 in 1 weighing function 
(called tared weighing).  The 2 in 1 function enables the weight of babies and small 
children to be determined while an adult holds them.  
a. Identify a suitable area that is flat for horizontal placement of the scale.  
b. Press the start key with no load on the scale.  The scale is ready for use when it 
sets to 0.00.  
i. If necessary, switch the weight display to KG: hold down the 2 in 1 key for 
about 3 seconds. Press the start key with no load on the scale.  Wait until 
the display shows 0.00. 
Seca 874 Scale 
1) Remove scale from bag. 
2) Be sure that the scale is placed on a flat, hard, even surface. All 4 legs of the scale 
should make contact with the ground surface, without wobbling. It may be helpful to 
place a piece of plywood on the ground underneath the scale.  
3) When batt appears in the display, you should change the batteries.  Remove the 
old batteries and insert 6 new batteries.   
Dismantling the ShorrBoard 
1) Stand the board upright: face the board and step on the base with one foot to 
keep it stable. 
2) Slide the head/footpiece into the base of the main board. 
3) Release the clasp on the back of the extension piece and remove it.  Push 
the clasp FLAT against the extension piece. 
4) To attach the extension piece to the main board, turn the front of the 
extension piece inward and place it against the front of the main board.  
Make sure that all sides of the extension piece are straight and in line with 
the main board. 
5) Push on the bolt that is on the back of the extension piece and screw it into 
the main board.   
6) Put the board back inside of the carrying case for storage until your next use.   


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
19 
c. Ask the adult to remove his/her shoes and stand in the middle of the scale 
without the child.  S/he should remove any long garments, as these can cover 
the display and also lead to variable measurements.   
d. After the adult’s weight appears on the display, tell him/her to remain standing on 
the scale.  Press the 2 in 1 key to activate the function. 
e. The scale stores the weight of the adult and the display returns to zero. When 
0.00 and NET appear in the display, hand the child to the adult.  The scale will 
determine the weight of the child.  Once the value is stable for about 3 seconds, 
the weight is measured.   
i. Note: If an adult is very heavy (e.g. more than 100 kg) and the baby’s 
weight is relatively low (e.g. less than 2.5 kg), the baby’s weight may not 
register on the scale.  In such cases, have a lighter person hold the baby 
on the scale. 
f. The positioner will clearly call out the child’s weight to the recorder.   
g. Record the child’s weight to the nearest 0.01 kg.  
h. Repeat the measurement 2 more times. Note that only the baby needs to be 
removed from the scale; the adult should remain on the scale the entire time. 
i. 
To turn off the 2 in 1 function, press the 2 in 1 key. The 2 in 1 function remains 
on until you press the 2 in 1 key again, or until the scale switches off 
automatically. 
 
2. If the child is able to stand on the scale, you will weigh the child alone.  Talk with the 
child about the need to stand still.  Communicate with the child in a sensitive, non-
frightening way. 
a. Press the start key with no load on the scale.  The scale is ready for use when it 
sets to 0.00. 
b. Ask the child to stand in the middle of the scale.  Once on the scale, the child 
must stand still.  The HOLD function is automatically activated for weights over 
1.5 kg/3.3 lbs.  The display flashes until a stable weight has been measured.  
The display is then frozen until the next weighing operation.   
i. Note: If the child jumps on the scale or won’t stand still, you will need to 
use the tared weighing procedure instead. 
c. The positioner will clearly call out the child’s weight to the recorder.  
Record the child’s weight to the nearest 0.01 kg.  
d. Repeat the measurement 2 more times. Have the child move completely off the 
scale and then stand again on the scale. 
 
If no further weighing operations are performed, the scale switches off automatically after 2-3 
minutes. 
 
Measuring Mid-Upper Arm Circumference (MUAC) 
Scale Calibration 
In order to monitor the calibration of the scales over time, each team will weigh a 5 kg test 
weight at the beginning and end of the day.  


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
20 
The child’s MUAC will be measured three times. MUAC measurements will be taken at the 
midpoint of the left arm between the tip of the shoulder and the tip of the elbow using non-
stretch MUAC tapes.  
 
1. First, find the approximate midpoint of the upper arm. Have the 
child stand up straight with feet together, and the right arm bent 90 
degrees at the elbow, palm facing up.  The examiner is positioned 
behind the child. If it is helpful, mark the midpoint with a permanent 
marker.  
2. To measure mid-upper arm circumference, have the child stand up straight with the 
arms relaxed at the sides.  The examiner will stand facing the child’s right side.  The 
measuring tape is placed around the upper arm at the marked 
point.   
3. Wrap the tape around the arm, pulling it to lie flat against the 
surface of the skin.  Be careful not to pull the tape too tightly 
(to compress the skin).   
4. The line for reading measurements is clearly labeled on the 
MUAC tape (READ (cm)). Read the number aligned with the 
measurement line on the tape. Upon measuring, the 
examiner will clearly call out the number to the recorder.  
Record to the nearest 0.1 cm (0.1 cm = 1 mm).  
5. Keeping the child in place, release the MUAC strip. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
21 
3.3. 
Malaria Rapid Diagnostic Test 
 
Malaria infection status will be assessed on all enrolled children using a rapid diagnostic test 
(RDT) at baseline and 8 weeks after admission into the nutritional program. At this point, we will 
also take the child’s temperature. 
 
Supplies 
• 
Mobile data collection device & accessories 
• 
RDT test packet 
• 
Alcohol swabs 
• 
Gloves 
• 
Lancet 
• 
Buffer 
• 
Timer 
 
Conduct the Malaria RDT 
1. Check the expiry date on the test packet. If the expiry date has passed, choose another 
packet that has not yet expired. 
2. Put on the gloves. Use new gloves for each patient. 
3. Open the packet and remove: 
a. The test 
b. The capillary tube 
c. The desiccant sachet 
4. Write the patient’s name and study ID number on the test 
5. Open the alcohol swab. Grasp the 4th finger on the patient’s left hand. Clean the finger 
with the alcohol swab. Allow the finger to dry before pricking. 
6. Open the lancet. Prick patient’s finger to get a drop of blood. 
7. Discard the lancet into an appropriate sharps receptacle immediately after pricking the 
finger. 
8. Use the capillary tube to collect the drop of blood. 
9. Use the capillary tube to put the drop of blood into the square hole on the test marked 
“A.” 
10. Discard the capillary tube into an appropriate sharps receptacle 
11. Add 6 drops of buffer into the round hole marked “B.” 
12. Wait 15 minutes after adding buffer 
13. Read test results. Do NOT read the test sooner than 15 minutes after adding the buffer. 
You may get false results 
14. How to read the test results: 
a. POSITIVE: a line near letter “C” and a line near letter “T” means the patient is 
positive for malaria. 
 
i. The test is positive even if the line near “T” is faint 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
22 
 
b. NEGATIVE: a line near letter “C” and NO LINE near letter “T” means the patient 
does NOT have malaria 
 
c. INVALID RESULT: NO LINE near letter “C” and one or no line near letter “T” 
means the test is INVALID 
 
i. Repeat the test using a new RDT and a new lancet if no control line 
appears 
15. Dispose of gloves, alcohol swab, desiccant sachet, and packaging 
16. Record the test result in the mobile application. 
 
 
3.4. 
Rectal swab collection 
 
Rectal swabs will be collected at baseline and at week 8 in a random subset of children. 
 
Procedure 
The test will require that the child’s parent and examiners work together to obtain a good 
sample.  Is it important to describe the test to the parent so that they can best assist with 
keeping the child still during the procedure. 
 
Rectal swabs can be collected in the following way:  
1. Put on a clean pair of gloves. 
2. Partially open the fecal swab package and remove the top section of the collection vial 
(this can be discarded). 
3. Position the child: 
• 
Lie the child on his/her back, hold legs in the air (it is useful to have assistance). 
• 
Or have the child lay on his/her stomach across the mother/guardian’s lap 
4. Remove the swab from the package. Take care that the cotton tip is not touched.  If it is 
touched, throw the swab away and begin with a new one. 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
23 
5. Insert the tip of the swab into the child’s anus only as far as needed to contact fecal 
material (1-3cm) and rotate 180 degrees.  The tip should be a brownish color when 
removed. 
6. Place swab into the preservative in the collection tube. Make sure the swab is fully 
submerged in the liquid preservative and then break the swab off using the pre-scored 
breaking point.  
7. Screw the cap back on the tube and make sure that it’s tightened. Wrap the area where 
the cap meets the tube with Parafilm to ensure that the sample will not leak, and then 
place the tube into the appropriate sample box.  
• 
If the swab cannot be broken off while the tip is fully submerged in the liquid, try 
twirling the swab in the liquid first (to release the contents of the sample into the 
preservative) before breaking it off. Avoid rubbing the sample on the tip of the 
swab off on the side of the tube where there is no liquid. 
8. Place a random number label on the collection tube. 
9. Place the tube the rectal swab container. 
10. Swab storage for Genetic analysis: Store samples at room temperature. According to the 
manufacturer, the preservative in the tube will preserve DNA for 5 months at room 
temperature (7 days for RNA), and thereafter can be frozen (-20°C or -80°C) for long-
term storage. 
 
 
Materials for Rectal Swab Collection 
Swab 
An individually-wrapped Copan flocked swab with a plastic shaft will be used to collect the rectal 
swab and then placed into a Zymo transport medium.   
 
Sample Tube with Media 
The specimen will be in a sterile Stool Nucleic Acid Collection and Transport Tube containing 
Zymo research Transport Medium with a cap that will be tightened firmly. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
24 
3.5. 
Vital Status 
 
Vital status will be recorded at all follow-up visits, including whether the child is alive, has died, 
or has moved. Date of death and location of move will be recorded. 
 
3.6. 
Clinical examination 
 
Outcomes of clinical examinations will be collected at enrollment, weekly follow-up visits, and at 
week 8. Clinical examinations will be conducted according to the standard of care in the 
management of SAM. Recorded outcomes include diagnoses made and treatments 
given/recommended. 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
25 
4. STUDY MEDICATION 
Children enrolled in the study will be offered weight-based, directly observed, oral suspension 
azithromycin or a short course of oral amoxicillin. We will monitor adverse events following 
treatment as described in Section 5.  
 
 
Study Medication Description  
 
Zithromax® for oral suspension is supplied in bottles containing azithromycin dehydrate powder 
equivalent to 1200mg per bottle and the following inactive ingredients: sucrose; tribasic  
anhydrous sodium phosphate; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and 
flavoring including spray dried artificial cherry, crème de vanilla, and banana.  After constitution, 
a 5mL suspension contains 200mg of azithromycin. 
 
 
The oral amoxicillin routinely used at each CSPS for treatment of uncomplicated severe acute 
malnutrition will be used for this trial. 
 
Dosage Information 
 
Azithromycin will be administered as a single dose, in oral suspension form for children. Dosing 
will follow the WHO recommendations for treatment of active trachoma: 
• 
Single dose of 20mg/kg in children (up to the maximum adult dose of 1g)  
 
Individuals who are allergic to macrolides/azalides will not be treated. 
 
Oral amoxicillin (80 mg per kilogram of body weight per day, divided into two daily doses) will be 
administered for 7 days. The first dose will be administered by the study nurse, who will teach 
the caregiver how to administer the medication at home. The remaining doses will be 
administered by the caregiver. 
 
 
Medication Procurement 
 
Azithromycin and amoxicillin will be purchased locally in Burkina Faso by the study team. 
Enrolled participants will incur no costs associated with the study medication.  
 
Medication Quality Control 
 
Study medication will be stored at each site prior to use.  The CRSN study team and site staff 
will regularly check and record the study medication expiration dates.  The expiration dates on 
the medication containers will be strictly monitored and all expired study medicine will be 
discarded appropriately. The study coordinator will work with each health facility to ensure that 
they have appropriate stock of all study medications. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
26 
5. ADVERSE EVENTS 
 
Parents or guardians of enrolled children will be instructed to report any adverse events 
experienced within the 7 days following the enrollment visit, by phone or in person. At all follow-
up visits, study staff will inquire about the child’s experience of adverse events, including if the 
child had any of the following symptoms: 
• 
Fever 
• 
Diarrhea 
• 
Vomiting 
• 
Abdominal pain 
• 
Skin rash 
• 
Constipation 
 
The study team will assess whether the parent or guardian sought care for the child since the 
last visit and if so, what the reason was for the health care visit and if the child was hospitalized. 
 
Serious adverse events will be defined as death, hospitalization, or any other life-threatening 
situation. Serious adverse events will be reported to the Medical Monitor within 24 hours. The 
study team member conducting the follow-up visit will email the CRSN Principal Investigator, 
who will immediately email the Medical Monitor and the UCSF study team. The Medical Monitor 
will make a determination as to whether the event could be reasonably considered to be related 
to the study drug and will report the results of this determination to the study investigators and 
the DSMC as needed. Information on all adverse events, serious and non-serious, will recorded 
on data collection forms through the mobile application.   
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
27 
6. DATA COLLECTION, MANAGEMENT, AND SECURITY  
 
6.1. 
Data Collection 
Data will be collected on enrolled children at baseline (time of enrollment), and follow-up weeks 
1- 8. Written informed consent will be collected on paper and the study nurse will record 
treatment administration on paper. All other data will be collected electronically on mobile 
devices using the Interviewer mobile application by Survey Solutions. Data to be collected are 
outlined in Figure 1 and Section 2.5. 
 
6.2. 
Data Management and Security  
Electronic data will be uploaded daily to a secure, password-protected, cloud-based server 
hosted by Survey Solutions. All devices used for data collection will be password-protected, as 
will the mobile application itself. Paper forms will be stored in locked cabinets accessible only by 
specific study team members at each enrollment site. 
 
No identifiers will be collected electronically. Study data will only be accessible by study team 
members and investigators in order to protect confidentiality. 
 
6.3. 
Data Quality and Monitoring  
All study team members collecting data will undergo an initial training to learn how to use the 
mobile devices as well as best practices for data collection. Data collection will be monitored on 
a weekly basis by the study team using dashboards created on Survey Solutions web-based 
platform. Concerns over data quality and completeness will be relayed to the local study team 
by email, and refresher trainings and/or additional supervision of data collection by local 
investigators will be planned as needed. The study team will send quarterly progress reports to 
the DSMC, including aggregate data on enrollment and follow-up status, weight gain, nutritional 
recovery, and adverse events. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
28 
7. PROTECTION OF HUMAN SUBJECTS 
 
Before any study procedures are implemented, the study team will obtain Institutional Review 
Board (IRB) approval from committees at UCSF and CRSN. In addition, local study team 
members will approach each potential enrollment site to describe the study and obtain their 
consent to participate as a study site. At the individual level, study personnel will obtain written 
informed consent from at least one parent or guardian for all study activities. If, at any time, a 
parent or guardian elects to withdraw a child from the study, they will be free to do so. 
Individuals who withdraw will be offered the same standard of care outside the study. 
 
7.1. 
Institutional Review Board Approval 
 
University of California, San Francisco (UCSF) Committee on Human Research 
UCSF’s Committee on Human Research will annually review the study protocol for ethical 
approval. 
 
Comité d’Ethique du Burkina Faso   
The study protocol will be reviewed and granted ethical approval by the Comité d’Ethique du 
Burkina Faso in Nouna before any study activities begin. 
 
 
7.2. 
Informed Consent 
Study personnel fluent in relevant local languages will approach parents or guardians of eligible 
children at the enrollment site. In a private setting, the study team member will explain the 
objectives, risks, and benefits of the study as well as detailed information about what study 
participation entails for the child and the parent or guardian. The study team member will clarify 
that participation in the study is voluntary, that participation may be stopped at any time, and 
that all collected data will be kept confidential and securely stored. The study team member will 
ensure comprehension by inviting the parent or guardian to ask questions and will provide time 
for the parent or guardian to consider participation. When providing consent, both the study 
team member and the parent or guardian will sign two copies the consent document. One copy 
will be given to the parent or guardian and the other will be kept for study reference. 
 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
29 
8. DATA AND SAFETY MONITORING COMMITTEE 
 
The Data and Safety Monitoring Committee (DSMC) will consist of independent experts in 
biostatistics, epidemiology, child health and nutrition, and/or global public health. 
 
The DSMC will be empaneled prior to the beginning of the study. The committee will meet once 
prior to the start of the study and at the study’s conclusion. All study protocols will be subject to 
review and approval by Institutional Review Boards at UCSF and CRSN, and by the DSMC. 
Serious adverse events will be reported to the DSMC based on the determination of the Medical 
Monitor. Committee members will monitor any severe or unexpected trend that threatens the 
safety of study participants. Quarterly progress reports will be submitted to the DSMC. Enrollment 
progress will be reviewed after 1 month to assess feasibility. Stopping guidelines will be agreed 
upon prior to the start of the study, and the DSMC will be authorized to end the study if they deem 
necessary.  
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
30 
9. STATISTICAL METHODS 
 
9.1. 
Sample Size and Power 
 
Specific Aim 1 We assume that inclusion of 300 children (150 randomized to each arm) will 
provide 80% power to detect a 27% increase in weight gain (g/kg/day) in children receiving 
azithromycin compared to children receiving  amoxicillin at an alpha of 0.05. Assumptions for 
this calculation were based on the pattern of weight gain reported in a trial of routine amoxicillin 
for uncomplicated SAM in Niger comparing children receiving amoxicillin to placebo over time.5 
We assumed an average weight gain of 4.9 g/kg/day in the  amoxicillin arm, with a standard 
deviation of 3.9 g/kg/day, and loss to follow-up of 10%. A 27% increase corresponds to a mean 
difference in weight gain of 1.3 g/kg/day, or an average weight gain of 6.2 g/kg/day in the 
azithromycin arm. 
 
This calculation was performed in Stata using the following command: 
 
power twomeans 4.9, sd(3.9) alpha(0.05) power(0.8) n(270) 
 
Specific Aim 2. Inclusion of 300 children (150 randomized to each arm) will provide 80% power 
to detect an 15 percentage point difference in the proportion of children achieving nutritional 
recovery in the azithromycin arm compared to the  amoxicillin arm. Assumptions for this 
calculation were based on nutritional recovery reported in the amoxicillin arm of a trial of routine 
amoxicillin for uncomplicated SAM in Niger.5 We assumed that 66% of children in the oral 
amoxicillin arm would achieve nutritional recovery and a loss to follow-up of 10%. 
 
This calculation was performed in Stata using the following command: 
 
power twoproportions 0.66, alpha(0.05) power(0.8) n(270) 
 
 
9.2. 
Statistical Analysis 
 
Baseline characteristics. Characteristics of the study population collected at baseline will be 
summarized using frequencies and percentages for categorical variables and means and 
standard deviations or medians and inter-quartile ranges for continuous variables. Baseline 
characteristics will be compared by treatment arm using Fisher’s exact test for categorical 
variables and t-tests or Wilcoxon rank-sum tests for continuous variables. 
 
Specific Aim 1. The primary analysis will compare weight gain velocity (g/kg/day) between 
groups over the 8-week follow-up period,. We will estimate mean differences and 95% 
confidence intervals for the difference using a linear regression model with an indicator for study 
group. 
 
E[𝑌 | 𝑋= 𝑥] = 𝛽! + 𝛽"𝑋+ 𝑒 
Where: 
• 
𝑌 = weight gain velocity from enrollment to 8 weeks  
• 
𝑋 = binary indicator for treatment group (X=1 for azithromycin, X=0 for a short course of 
oral amoxicillin) 
• 
𝛽" = difference in weight gain velocity between the azithromycin group compared to a 
short course of oral amoxicillin group 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
31 
• 
𝑒 ~ 𝑁 (0, 𝜎$)  
 
 
Specific Aim 2. The primary analysis will compare nutritional recovery by 8 weeks from 
baseline by arm. We will use log-binomial regression for this analysis to estimate the risk ratio. 
We will use the following model: 
 
log[𝑃(𝑌= 1|𝑋" = 𝑥"] = 𝛽! + 𝛽"𝑋" + 𝑒 
 
Where: 
• 
𝑌 = binary indicator for nutritional recovery by 8 weeks (Y=1 for recovered, Y=0 for not 
recovered) 
• 
𝑋 = binary indicator for treatment arm (X=1 for azithromycin, X=0 for a short course of 
oral amoxicillin) 
• 
𝑒%! = relative risk of nutritional recovery in azithromycin arm compared to a short course 
of oral amoxicillin arm 
• 
𝑒 ~ 𝑁 (0, 𝜎$)  
 
If the log-binomial model fails to converge, we will use a modified Poisson model with robust 
standard errors as an alternative. 
 
Secondary outcomes. 
 
Time to event outcomes (time to recovery and time to mortality) will be assessed visually using 
Kaplan-Meier curves and compared by arm using the log-rank test. 
 
Binary outcomes will be analyzed using modified Poisson regression for rare outcomes (e.g. 
mortality) or log-binomial regression for common outcomes (e.g. malaria), using models similar 
to the one described above for Specific Aim 2. 
 
Anthropometric assessments will be analyzed using linear models as described for Specific Aim 
1, with correction for baseline values. For anthropometric assessments, z-scores will be 
calculated based on the 2006 WHO Child Growth Standards. Anthropometric z-scores will be 
analyzed as continuous variables and secondary analyses will explore categorization. 
 
All analyses will be intention-to-treat. A significance level of 0.05 for inference and 95% 
confidence intervals will be reported for all effect estimates. All analyses will be conducted using 
R (R Foundation for Statistical Computing, Vienna, Austria). For all models, model diagnostics 
will be conducted to assess appropriate fit. 
 
Missing data. 
 
If ≤10% of enrolled children is missing outcome data, complete case analyses will be 
conducted. If >10% of enrolled children are missing outcome data, inverse probability weighting 
will be used to weight complete cases by the inverse of an estimate of the probability of an 
outcome being observed as a sensitivity analysis. Weights will be constructed with the following 
baseline characteristics chosen as factors likely to predict follow-up: SES, distance from CSPS, 
WHZ, and MUAC. 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
32 
REFERENCES 
 
1. 
Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and 
overweight in low-income and middle-income countries. The Lancet. 
2013;382(9890):427-451. 
2. 
Page AL, de Rekeneire N, Sayadi S, et al. Infections in children admitted with 
complicated severe acute malnutrition in Niger. Plos One. 2013;8(7):e68699. 
3. 
Fishman SM, Caulfield LE, de Onis M, et al. Childhood and maternal underweight. In: 
Ezzati M, Lopez AD, Rodgers A, Murray CJL, eds. Comparative Quantification of Health 
Risks Global and Regional Burden of Disease Attributable to Selected Major Risk 
Factor. Vol 1. Geneva: World Health Organization; 2004:39-163. 
4. 
Trehan I, Goldbach HS, LaGrone LN, et al. Antibiotics as part of the management of 
severe acute malnutrition. Malawi Med J. 2016;28(3):123-130. 
5. 
Isanaka S, Langendorf C, Berthe F, et al. Routine Amoxicillin for Uncomplicated Severe 
Acute Malnutrition in Children. N Engl J Med. 2016;374(5):444-453. 
6. 
Trehan I, Schechtman KB, Manary MJ. Amoxicillin for Severe Acute Malnutrition in 
Children. N Engl J Med. 2016;375(2):191. 
7. 
Berkley JA, Ngari M, Thitiri J, et al. Daily co-trimoxazole prophylaxis to prevent mortality 
in children with complicated severe acute malnutrition: a multicentre, double-blind, 
randomised placebo-controlled trial. Lancet Glob Health. 2016;4(7):e464-473. 
8. 
Keenan JD, Bailey RL, West SK, et al. Azithromycin to Reduce Childhood Mortality in 
Sub-Saharan Africa. N Engl J Med. 2018;378(17):1583-1592. 
9. 
Rutebemberwa E, Mpeka B, Pariyo G, et al. High prevalence of antibiotic resistance in 
nasopharyngeal bacterial isolates from healthy children in rural Uganda: A cross-
sectional study. Ups J Med Sci. 2015;120(4):249-256. 
10. 
Lazzerini M, Tickell D. Antibiotics in severely malnourished children: systematic review 
of efficacy, safety and pharmacokinetics. Bull World Health Organ. 2011;89(8):594-607. 
 
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
33 
REVISIONS HISTORY 
 
• 
June 4 2020: change inclusion criteria from “Has not been admitted to a nutritional 
program for the treatment of SAM in the 3 preceding months” to “Has not been admitted 
to a nutritional program for the treatment of SAM in the 2 preceding weeks” 
• 
June 30 2020: Definition of recovery modified to fit the national program. 
• 
Error in the nutritional recovery number  
 
 


SAM Pilot Trial MOP 
Version 3.6, Revised March 2021 
 
34 
APPENDIX 
 
Appendix 1. Informed Consent Documents 
Appendix 2. Study Forms 
Appendix 3. Appetite test 
Appendix 4. Standard medical protocol for severe malnutrition