Effectiveness of a reduced dose of ready-to-use therapeutic food (RUTF) in the management of uncomplicated severe acute malnutrition (SAM)

ISRCTN	ISRCTN15258669
DOI	https://doi.org/10.1186/ISRCTN15258669

Submission date: 11/09/2021
Registration date: 25/01/2022
Last edited: 15/05/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
More than 47 million children were acutely malnourished worldwide before the COVID-19 pandemic. Disruptions in economic systems, reduced access to health and nutrition services have led to a 20% increase (about 10.4 million) in the number of children who will be acutely malnourished by 2021, mainly in low- and middle-income countries (Asia and Sub-Saharan Africa, including the Democratic Republic of Congo (DRC)).
The treatment of severe acute malnutrition (SAM) without complications is done on a community basis using systematic medical and nutritional treatment (distribution of Ready-to-use Therapeutic Foods, RUTF) according to the strategy of community-based management of acute malnutrition (CBM).
The aim of this study is to evaluate the effectiveness of a reduced dose of RUTF on the velocity of weight gain in children aged 6-59 months suffering from severe acute malnutrition.

Who can participate?
All medically uncomplicated SAM children aged 6-59 months.

What does the study involve?
Children enrolled in this study will be divided into two groups: control and intervention. For the first 2 weeks, all children in both groups will receive the same dose of standard RUTF. From the third week onwards, the dose of RUTF will be reduced for the intervention group according to their weight.

What are the possible benefits and risks of participating?
The child will be treated against malnutrition and will receive the same care as that usually provided by the health center. The risks are no weight gain, weight loss or allergies to the products used in the manufacture of the Ready-to-Use Therapeutic Food. In case of risk, the study is covered by insurance and the principal investigator will ensure the treatment and compensation of any adverse effect observed in the child following this study, linked to the use of the nutritional product and/or research procedures, throughout the duration of the study.

Where is the study run from?
Université de Kinshasa (DRC)

When is the study starting and how long is it expected to run for?
February 2021 to August 2022

Who is funding the study?
Foreign, Commonwealth & Development Office (FCDO) of the UK Government (updated 28/03/2022, previously: Action Against Hunger (DRC); updated 31/01/2022, previously: Foreign, Commonwealth & Development Office (FCDO) of the UK Government)

Who is the main contact?
Julien Ntaongo Alendi
j.ntaongo@gmail.com

Contact information

Mr Julien Ntaongo Alendi
Scientific

Campus
Université de Kinshasa
Kinshasa
BP 127, Kinshasa XI
Congo, Democratic Republic

ORCID ID	0000-0003-0624-7189
Phone	+243 826083359
Email	j.ntaongo@gmail.com

Study information

Study design	Interventional randomized controlled non-inferiority trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Community
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a participant information sheet
Scientific title	Effectiveness of a reduced dose of ready-to-use therapeutic food (RUTF) in children under 5 years of age suffering from uncomplicated severe acute malnutrition (SAM) compared to a standard dose: a randomized, controlled, non-inferiority trial in real-life conditions in Bonzola and Nzaba Health Zones, city of Mbuji-Mayi, Kasai Oriental, DRC, in 2021
Study acronym	EfRAMAS
Study hypothesis	Children receiving the reduced dose will have the same weight gain from admission to discharge as children receiving the standard dose of Ready-to-Use Therapeutic Food (RUTF) with a non-inferiority margin of 0.5 g/kg/d. Secondary assumptions : 1. Children receiving the reduced dose of RUTF will have the same performance indicators (cure rate, death, dropout, relapse) as those receiving the standard dose 2. Children receiving the reduced dose of RUTF will have the same length of stay as those receiving the standard dose 3. Children receiving the reduced dose of RUTF will have the same psychomotor development as those receiving the standard dose 4. Treatment with the reduced protocol of RUTF will be less expensive than treatment with the standard dose.
Ethics approval(s)	Approved 31/07/2021, Ethics Committee of the School of Public Health, University of Kinshasa (Campus Université de Kinshasa, DRC; +243 817 493 194; espsec_unikin@yahoo.fr), ref: ESP/CE/127/2021
Condition	Severe acute malnutrition without medical complications
Intervention	Current intervention as of 31/01/2022: This study is a non-inferiority randomized controlled trial. Randomization will be done at the individual level in each of the 14 study health areas. Block randomization of varying sizes will be used. After randomization, participants will be randomly assigned to either the control or intervention group. Each participant will receive the dose of RUTF corresponding to the group to which he/she belongs: standard dose for the control group and reduced dose for the intervention group. Both groups will receive the same dose of RUTF for the first 2 weeks. Then in the intervention group, the reduction in the dose of RUTF will occur from the third week of treatment. The intervention will be started concomitantly in both groups. The dose reduction will range from 13 to 53% depending on weight. In addition to nutritional management, participants will also receive routine medical treatment. After recovery (according to the admission criteria, if P/T ≥- 1.5 z-score at two consecutive weighings, and PB ≥125 mm and absence of nutritional oedema for 14 days), follow-up of participants will be performed every 15 days until 3 months after discharge as planned in the national protocol. During this follow-up, the children will receive medical treatment if needed according to symptoms (malaria, etc) and a nutritional product (fortified flour or Ready-to-use Supplementary Food [RUSF]) if available. Children who develop complications during treatment will be referred to the Intensive Therapeutic Nutritional Unit (UNTI) and then reintegrated into their study group after the complication has been resolved. During the course of the study, a qualitative survey using focus groups, in-depth interviews, and field observations will assess the degree of acceptance of the reduced dose of RUTF by the local communities. An economic evaluation of the cost of treatment will be done during the study by comparing the reduced dose approach to the standard dose approach. A sub-study will document the evolution of the Psychomotor Development (DPM) status of children from admission to discharge and at 6 months follow-up. This sub-study aims to assess the proportion of children with psychomotor developmental delay (PDD) and to monitor their progress during treatment. Psychomotor developmental delay (PDD) refers to impairments in the acquisition of skills and competencies in the areas of language, cognitive, motor, and social interaction. PDD corresponds to a score of less than 70% in two of the four domains of Psychomotor Development (DPM). Previous intervention: This study is a non-inferiority randomized controlled trial. Randomization will be done at the individual level in each of the 14 study health areas. Block randomization of varying sizes will be used. After randomization, participants will be randomly assigned to either the control or intervention group. Each participant will receive the dose of RUTF corresponding to the group to which he/she belongs: standard dose for the control group and reduced dose for the intervention group. Both groups will receive the same dose of RUTF for the first 2 weeks. Then in the intervention group, the reduction in the dose of RUTF will occur from the third week of treatment. The intervention will be started concomitantly in both groups. The dose reduction will range from 13 to 53% depending on weight. In addition to nutritional management, participants will also receive routine medical treatment. After recovery (according to the admission criteria, if P/T ≥- 1.5 z-score at two consecutive weighings, and PB ≥125 mm and absence of nutritional oedema for 14 days), follow-up of participants will be performed every 15 days until 3 months after discharge as planned in the national protocol. During this follow-up, the children will receive medical treatment if needed according to symptoms (malaria, etc) and a nutritional product (fortified flour or Ready-to-use Supplementary Food [RUSF]) if available. Children who develop complications during treatment will be referred to the Intensive Therapeutic Nutritional Unit (UNTI) and then reintegrated into their study group after the complication has been resolved. During the course of the study, a qualitative survey using focus groups, in-depth interviews and field observations will assess the degree of acceptance of the reduced dose of RUTF by the local communities. An economic evaluation of the cost of treatment will be done during the study by comparing the reduced dose approach to the standard dose approach.
Intervention type	Supplement
Primary outcome measure	Current primary outcome measure as of 25/03/2022: Weight gain velocity (g/kg/d) measured using scales weekly from admission to discharge Previous primary outcome measure as of 31/01/2022: Weight (kg) measured using scales weekly between admission and discharge, and then fortnightly after discharge for up to 3 months Previous primary outcome measure: Weight (kg) measured using scales at admission, at discharge, and then every 15 days up to 3 months
Secondary outcome measures	Current secondary outcome measures as of 31/01/2022: 1. Acceptance of a reduced dose during SAM treatment by health care personnel and the community measured using discussion groups, in-depth interviews, and direct observation using interview and focus group guides as well as observation grids in November 2021. This survey will assess the perceptions of families and health care providers on the amount of RUTF received, consumption and use practices, and their attitude towards a possible dose reduction. 2. Relapse rate measured as the proportion of children treated for SAM and declared cured who revert to SAM within 3 months of completing treatment, using anthropometric measurements including weight (kg), height (cm), and arm circumference (mm) taken using scales, height chart and tape measure at 3 months after treatment 3. Psychomotor development measured using the Psychomotor Development Index (PDI) at admission, discharge, and 6 months after treatment 4. Duration of the edema melting measured as the number of days taken for the lower limbs of SAM children to return to their normal volume using a tape measure at all study visits 5. Length of stay measured as the number of days between admission and discharge (with discharge occurring at PB≥12.5 cm and/or PT ≥-3 z-score and/or edema melt). The maximum length of stay is 12 weeks or 3 months 6. The cure rate measured as meeting the cure criteria according to admission category during two consecutive visits and no edema during two visits in two consecutive weeks measured using PT index (≥-1.5) or PB (≥125 mm) and edema at all study visits 7. The dropout rate measured as the proportion of children confirmed alive who missed two successive visits, at all study visits. The abandonment is confirmed once after the visit of the RECO which confirms that the child is alive despite his 2 absences during the weekly visits. Children who have been abandoned will be followed up to 3 months after the abandonment. For children who can be found, offer the caregivers a small snack at a single appointment 3 months after abandonment to take the anthropometric measurements. 8. Death rate measured as the proportion of children randomized to the study who died during the intervention at any time 9. Cost savings (average cost saved and cost saved per child treated) measured by comparing the cost of treatment for children in care and declared cured in the two groups using the direct costs of drugs and RUTF (purchase, transport, transport, and storage) to assess the cost for each child, the HR costs involved in the care, the non-medical costs (food and transport. beneficiaries), and indirect costs (loss of productivity) throughout the trial 10. Prevalence of stunting and being underweight measured using anthropometric measurements including weight (kg), height (cm), and arm circumference (mm) taken using scales, height chart, and tape measure at the end of the treatment. Previous secondary outcome measures: 1. Acceptance of a reduced dose during SAM treatment by health care personnel and the community: this involves assessing the perceptions of families and health care providers on the amount of RUTF received, consumption and use practices and their attitude towards a possible dose reduction. Assessed using a qualitative approach by organizing discussion groups, in-depth interviews and direct observation using interview and focus group guides as well as observation grids. This survey was conducted in November 2021 2. Relapse rate: the proportion of children treated for SAM and declared cured who revert to SAM within 3 months of completing treatment, assessed using anthropometric measurements including weight (kg), height (cm) and arm circumference (mm) taken using scales, height chart and tape measure 3. Psychomotor development: this sub-study aims to assess the proportion of children with psychomotor developmental delay (PDD) and to monitor their progress during treatment. Psychomotor developmental delay (PDD) refers to impairments in the acquisition of skills and competencies in the areas of language, cognitive, motor, and social interaction. PDD corresponds to a score of less than 70% in two of the four domains of Psychomotor Development (DPM) at admission, discharge, and 6 months after treatment. In this substudy, it is expected that the DPM of children with Psychomotor Development Delay (RDPM) will improve after treatment simply as a result of medical and nutritional intervention without any specific action on the DPM during treatment.
Overall study start date	01/02/2021
Overall study end date	30/08/2022

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	59 Months
Sex	Both
Target number of participants	1000
Participant inclusion criteria	1. Children aged 6 to 59 months 2. Only one child per sibling included in the study 3. Severe acute malnutrition (weight-height index <-3 Z-score and/or mid-upper arm circumference <115 mm and/or bilateral edema (+: edema localized to the lower limbs; ++: edema localized to the lower and upper limbs) 4. Without medical complications 5. With conclusive appetite test 6. Living in the selected health zone 7. Consent to participate in the study (informed consent) 8. When there are several participants in the same sibling, only the first to be included in the study will be randomized. The others will automatically be included in the same group as the first one without being randomized and will not be taken into account in the analyses
Participant exclusion criteria	1. Inconclusive appetite test 2. Siblings of SAM children: any SAM child whose brother or sister (same father, same mother) is already enrolled in the study. Be careful, he/she will have to receive the same dose as his/her brother or sister outside the study in order not to create a bias with different doses within the same family 3. Declared allergy to peanut and/or milk 4. Previously treated for SAM in the past 6 months, including readmissions after program dropout, relapses and medical transfers 5. Malformation or disability or chronic pathologies that can affect food intake, such as cleft palate, cerebral palsy, trisomy 2, sickle cell anemia
Recruitment start date	19/08/2021
Recruitment end date	30/11/2021

Locations