ComPAS Low-WAZ RCT Mali

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Malnutrition in Childhood; Underweight; Acute Malnutrition in Infancy
• Intervention / Treatment: Dietary supplement: No nutritional treatment; Dietary supplement: Simplified dose of ready-to-use therapeutic food (RUTF); Dietary supplement: Standard dose of ready-to-use therapeutic food (RUTF)

• Study Type: Interventional
• Enrollment (Estimated): 1500
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Suvi T Kangas, MSc, PhD; Phone Number: +221 78 107 83 45; Email: suvi.kangas@rescue.org
• Study Contact Backup: Name: Césaire Ouedraogo, MD, PhD; Phone Number: +223 76 67 48 02; Email: cesaire.ouedraogo@rescue.org

Study Locations

• Mali
  • Koulikoro
    • Nara, Koulikoro, Mali
      • Dilly
    • Nara, Koulikoro, Mali
      • Gassambarou
    • Nara, Koulikoro, Mali
      • Goumbou
    • Nara, Koulikoro, Mali
      • Kaloumba
    • Nara, Koulikoro, Mali
      • Karfabougou
    • Nara, Koulikoro, Mali
      • Koira
    • Nara, Koulikoro, Mali
      • Koronga
    • Nara, Koulikoro, Mali
      • Madina-Kagoro
    • Nara, Koulikoro, Mali
      • Nara Central
    • Nara, Koulikoro, Mali
      • Sampaga
    • Nara, Koulikoro, Mali
      • Tiapato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 3 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control; no nutritional treatment administered	Dietary supplement: No nutritional treatment; no nutritional treatment will be provided to children in the control arm.
Experimental: Simplified treatment; children are provided with 1 sachet of RUTF until discharge	Dietary supplement: Simplified dose of ready-to-use therapeutic food (RUTF); 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.
Active Comparator: Standard treatment; 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); 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
subscapular skin-fold thickness in millimeters	this outcome is a continuous outcome. there are currently no internationally accepted standards for the skinfold measure of young children. we will thus report the mean and any other relevant data on this and discuss the results in light of past research.	2 and 6 months post-enrolment
proportion having developed a mid-upper-arm circumference <125mm	the proportion of children that exit the study with a MUAC<125mm at any point in time will be estimated. MUAC will be measured at each visit using a while MUAC tape with a precision of 1mm.	6 months post-enrolment
tricep skin-fold thickness in millimeters	this outcome is a continuous outcome. there are currently no internationally accepted standards for the skinfold measure of young children. we will thus report the mean and any other relevant data on this and discuss the results in light of past research.	2 and 6 months post-enrolment
fat-free mass in kg	this outcome is a continuous outcome obtained through bioelectrical impedance analysis and applying a suitable equation to obtain fat-free mass estimations from weight and impedance.	2 and 6 months post-enrolment
fat mass in kg	this outcome is a continuous outcome obtained through bioelectrical impedance analysis and applying a suitable equation to first obtain fat-free mass estimations from weight and impedance and then by substracting fat-free mass from weight.	2 and 6 months post-enrolment
fat-free mass index in kg/m2	this outcome is a continuous outcome obtained through bioelectrical impedance analysis and applying a suitable equation to obtain fat-free mass estimations from weight and impedance and indexing fat-free mass to height squared to adjust for differences in size.	2 and 6 months post-enrolment
fat mass index in kg/m2	this outcome is a continuous outcome obtained through bioelectrical impedance analysis and applying a suitable equation to first obtain fat-free mass estimations from impedance and weight and then substracting fat-free mass from weight and indexing the obtained fat mass to height squared to adjust for differences in size.	2 and 6 months post-enrolment
hemoglobin (g/l)	this is a continuous outcome and will be obtained through HemoCue measurement of peripheral blood	2 and 6 months
anaemia	this is a binary outcome and will be obtained through hemoglobin measurement of peripheral blood and categorising Hb<11g/l as anaemic.	2 and 6 months

Collaborators and Investigators

• Sponsor: International Rescue Committee
• Collaborators: Ministry of health, Mali; University of the Sciences, Techniques and Technologies of Bamako

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: randomized controlled trial; malnutrition; wasting; stunting; Mali; underweight; ready-to-use therapeutic food; acute malnutrition; weight-for-age z-score; mid-upper-arm circumference
• Additional Relevant MeSH Terms: Nutrition Disorders; Body Weight; Malnutrition; Thinness
• Other Study ID Numbers: H 1.00.033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators are planning on making data underlying publications available through on-line data repositories such as Zenodo. This data would be de-identified prior to sharing.
• IPD Sharing Time Frame: Study protocol, SAP and ICF will be published with the main results. The SAP will also be made available through clinicaltrials.gov prior to trial data collection completion. The study data underlying the key findings will be made freely available once analysis is complete and results published for the primary and secondary objectives and outcomes.
• IPD Sharing Access Criteria: Study protocol, SAP and ICF will be openly available via the publication. The study data will be made freely available from Zenodo or similar data repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No