ComPAS Low-WAZ RCT Mali

Study Overview
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Brief Summary
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Admissions criteria which treat children with only low mid-upper arm circumference (MUAC) or children with low weight-for-height z-score (WHZ) are not aligned with the evidence on which children are at risk of mortality. An analysis of community-based cohort data from Senegal found that a combination of weight-for-age z-score (WAZ) and MUAC criteria identified all children at risk of near-term death associated with severe anthropometric deficits. This finding has led to the suggestion that WAZ<-3 could be added as an independent admissions criterion for therapeutic feeding programs currently admitting children with MUAC<125 mm. However, there is little evidence to inform the debate about whether children with MUAC ≥125 mm and WAZ<-3 would benefit from treatment and, if so, what treatment protocol should be used. This study will address whether children with WAZ <-3 but MUAC ≥125 mm benefit from therapeutic feeding and whether a simplified protocol is at least as effective as the more complicated weight-based standard protocol for this population. The study will be a prospective, multi-center, individually randomized controlled trial (RCT). Children aged 6-59 months presenting with MUAC ≥125 mm and WAZ<-3 will be randomized to one of three study arms. The primary objective of this study is to assess whether therapeutic feeding with a simplified protocol (1 sachet RUTF/day) results in superior nutritional outcomes compared to no therapeutic feeding AND non-inferior nutritional outcomes compared to the WHZ and weight based dosing regimen currently used in CMAM treatment 2 months after diagnosis among children aged 6-59 months with MUAC ≥125 mm and WAZ<-3 . The primary outcome is the mean WAZ of children. Secondary outcomes include a) proportion of children with WAZ <-3, b) mean MUAC of children, c) proportion of children with MUAC < 125 mm, d) mean WHZ, mean HAZ, e) proportion of children with WHZ<-3 or HAZ<-3, f) change in WAZ, MUAC, WHZ, HAZ from enrolment to endpoint g) mean skinfold thickness measure.

Official Title
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Simplified Treatment of Children With Low WAZ in Mali. A Randomized Controlled Trial

Conditions
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Acute Malnutrition in Infancy, Acute Malnutrition in Childhood, Underweight

Intervention / Treatment
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* Dietary Supplement: Simplified dose of ready-to-use therapeutic food (RUTF)
* Dietary Supplement: Standard dose of ready-to-use therapeutic food (RUTF)
* Dietary Supplement: No nutritional treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 6 and 59 months MUAC ≥125 mm WAZ <-3 Living in the study catchment area Expects to be able to continue follow-up visits for next 6 months Exclusion Criteria: nutritional edema Known peanut or milk allergy Severe illnesses requiring inpatient level treatment (according to IMCI guidelines) Medical condition affecting food intake (lip and palate cleft, handicap etc.) Has already taken part in the study

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control<br>no nutritional treatment administered | Dietary Supplement: No nutritional treatment<br>* no nutritional treatment will be provided to children in the control arm.<br>|
| Experimental: Simplified treatment<br>children are provided with 1 sachet of RUTF until discharge | Dietary Supplement: Simplified dose of ready-to-use therapeutic food (RUTF)<br>* In the simplified arm all children receive the same dose: 1 sachet of RUTF/day. This until discharge from treatment. Recovery from treatment will be defined as WAZ>= -3 on 2 consecutive visits. A maximum of 12 treatment weeks are allowed before declaring non-response. Defaulting will be declared after 2 consecutively missed visits.<br>|
| Active Comparator: Standard treatment<br>children are provided nutritional treatment according to their weight-for-height z-score (WHZ) and their weight: children with a WHZ<-3 will receive 200kcal/kg/d of nutritional product until discharge children with a WHZ between -3 and -2 are provided with 1 sachet of RUTF until discharge children with a WHZ >= -2 will not be provided any nutritional treatment | Dietary Supplement: Standard dose of ready-to-use therapeutic food (RUTF)<br>* In the standard arm, children will receive different doses of RUTF depending on their WHZ category and weight. children with a WHZ<-3 will receive the equivalent of 200kcal/kg/d of RUTF until discharge. children with a WHZ between -3 and -2 will receive 1 sachet (500kcal) of RUTF per day until discharge. children with a WHZ>=-2 will receive no nutritional treatment. Recovery from treatment will be defined as WHZ>= -2 on 2 consecutive visits. A maximum of 12 treatment weeks are allowed before declaring non-response. Defaulting will be declared after 2 consecutively missed visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| weight-for-age z-score (WAZ) | the primary outcome is a continuous outcome: a higher WAZ indicates of a positive outcome. To construct WAZ at any point in time, children's age will be calculated based on their age at admission and their weight will be measured at each time point with 0.1kg precision. WAZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | 2 months after enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| weight-for-age z-score (WAZ) | the secondary outcome is a continuous outcome: a higher WAZ indicates a positive outcome. To construct WAZ at any point in time, children's age will be calculated based on their age at admission and their weight will be measured at each time point with 0.1kg precision. WAZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | 6 months after enrolment | 
| weight-for-age z-score (WAZ) <-3 | this outcome is binary: a higher proportion of WAZ<-3 indicates a negative outcome. To construct WAZ at any point in time, children's age will be calculated based on their age at admission and their weight will be measured at each time point with 0.1kg precision. WAZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | both at 2 and 6 months post-enrolment | 
| weight-for-height z-score (WHZ) | this outcome is a continuous outcome: a higher WHZ indicates a positive outcome. To construct WHZ at any point in time, children's height and weight will be measured at each time point: height with 0.1cm precision and weight with 0.1kg precision. WHZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | both at 2 and 6 months post-enrolment | 
| weight-for-height z-score (WHZ) <-3 | this outcome is binary: a higher proportion of WHZ<-3 indicates a negative outcome. To construct WHZ at any point in time, children's height and weight will be measured at each time point: height with 0.1cm precision and weight with 0.1kg precision. WHZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | both at 2 and 6 months post-enrolment | 
| height-for-age z-score (HAZ) | this outcome is a continuous outcome: a higher HAZ indicates a positive outcome. To construct HAZ at any point in time, children's age will be calculated based on their age at admission and their height will be measured at each time point with 0.1cm precision. HAZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | both at 2 and 6 months post-enrolment | 
| height-for-age z-score (HAZ) <-3 | this outcome is binary: a higher proportion of HAZ<-3 indicates a negative outcome. To construct HAZ at any point in time, children's age will be calculated based on their age at admission and their height will be measured at each time point with 0.1cm precision. HAZ will be calculated using zscore06 fonction in STATA that is based on the WHO growth reference data specific to each gender. | both at 2 and 6 months post-enrolment | 
| Mid-upper-arm circumference (MUAC) | this outcome is a continuous outcome: a higher MUAC indicates a positive outcome. MUAC will be measured using a while MUAC tape with a precision of 1mm. | both at 2 and 6 months post-enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute malnutrition, wasting, stunting, underweight, malnutrition, ready-to-use therapeutic food, randomized controlled trial, weight-for-age z-score, mid-upper-arm circumference, Mali