Clinical trial NCT03751475: Optimizing Acute Malnutrition Management in Children Aged 6 to 59 Months in Democratic Republic of Congo
Official title: Optimized and Simplified Management of Acute Malnutrition in Children Aged 6 to 59 Months: a Community-based Clinical Randomized Controlled Trial in the Democratic Republic of Congo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Acute Malnutrition
Moderate Acute Malnutrition
Child Malnutrition
Acute Malnutrition
Congo, The Democratic Republic of the
Africa
Randomized Clinical Trial
Keywords: Acute Malnutrition
Severe Acute Malnutrition
Moderate Acute Malnutrition
Child Malnutrition
Congo, The Democratic Republic of the
Randomized Clinical Trial
Africa
Lead sponsor: Alliance for International Medical Action
Sponsor class: OTHER
Collaborators: name: Ministry of Public Health, Democratic Republic of the Congo
name: The Innocent Foundation
name: University of Bordeaux
First posted: 2018-11-23
Enrollment: 896
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 parallel arms stratified on site and degree of acute malnutrition. 890 participants for the principal objective 480 participants with severe acute malnutrition for the secondary main objective
Primary purpose: TREATMENT

Brief summary: Acute malnutrition affects 51 million children under the age of 5 worldwide. Malnutrition contributes to nearly half of all child deaths each year, with the forms characterized by wasting or oedema (acute malnutrition) associated with the highest risk of death.

Although acute malnutrition is a continuum condition, it is arbitrarily divided into severe and moderate acute malnutrition (SAM, MAM) which are managed separately, with programs overseen by different UN agencies, and using different protocols and products. Such separation complicates delivery of care, contributes to high default and low coverage, and creates confusion among caregivers. Often treatment is only available for SAM children resulting in lives lost and costly hospitalisation that could be averted if nutritional support were available earlier in the wasting process. If we are to reduce the health and mortality burden from malnutrition, the effectiveness and cost-effectiveness of current protocols need dramatic improvements.

The dosage of Ready to Use Therapeutic Food (RUTF) for SAM (130-200 kcal/kg/d) has not changed since introduction of out-patient protocols in the mid-2000s. Children classified as SAM in these protocols are determined by three independent criteria: the presence of nutritional oedema or MUAC \< 115 mm or weight-height Z score \<-3. The RUTF dosage in these protocols is paradoxical in that the absolute amount of RUTF prescribed in the initial phases of treatment is often less than that given as the child nears recovery, because the number of packets in the weekly ration is determined by weight. However, rate of weight gain (g/kg/day) is highest in the first two weeks of treatment, and then plateaus - suggesting no benefit of increased RUTF amounts in the later phases of treatment. Progressive reduction seems to be a more rational use of RUTF.

The Optimizing treatment for acute MAlnutrition (OptiMA) strategy consists in simplifying management of acute malnutrition through the use of a single anthropometric admission criterion (mid upper arm circumference \[MUAC\] \< 125 mm or nutritional oedema) - one that best captures children's anthropometry related mortality risk- and by optimizing the use of RUTF by adapting doses to the nutritional recovery of the child. RUTF doses begin at 170 kcal/kg/d for the most severely wasted (MUAC \< 115 mm or oedema) and reduce to 75 kcal/kg/d as oedema resolves and MUAC increases \> 120 mm.

The investigators hypothesize that this strategy could double the number of children in care compared to current SAM programs without substantially increasing the amount of RUTF or staffing required while maintaining a recovery rate in line with current programs. OptiMA may also improve coverage and reduce the need for hospitalization through early identification of malnourished children.

The investigators propose to conduct a community-based non-inferiority clinical trial with individual randomization comparing the OptiMA strategy to the Democratic Republic of Congo standard nutritional protocol for SAM. Study children will be randomly assigned to the intervention arm or control arm - with children at MUAC \< 125 mm or oedema eligible for RUTF in the intervention arm and those meeting current WHO SAM definition eligible in the control group. All participants will be followed for 9 months post-randomization to assess non-inferiority as defined by a composite of three endpoints : alive, acceptable nutritional status (MUAC ≥ 125 mm and WHZ \>-3, no oedema) and no relapse to acute malnutrition for those who were treated with RUTF. The main secondary outcome will assess the non-inferiority of OptiMA RUTF dosing (170 kcal/kg/d) in children meeting current WHO SAM criteria compared to children with the same criteria in the control arm who will receive 130-200 kcal/kg/d.

Detailed description: The OptiMA strategy proposes a new malnutrition management approach, grounded in 3 main principles.

Firstly, the diagnosis of acute malnutrition is refined to target those at highest mortality risk within the CMAM definition of acute malnutrition (WHZ \< -2 or MUAC \< 125 mm or oedema), by targeting treatment to children with a MUAC \< 125 mm or oedema. The simplicity of MUAC measure allows families to screen children and check for oedema at home and identify malnourished children at an earlier stage. The diagnosis is quickly confirmed by clinicians at the health center. MUAC progression is also used to monitor recovery and determine discharge thus eliminating the discrepancies that occur when both MUAC and WHZ are used to diagnose acute malnutrition.

Secondly, RUTF dosage is rationalized, and calibrated to the child's degree of wasting. The WHZ tables and dosing tables are replaced by a single table that determines the child's RUTF ration based on MUAC category and weight. Larger rations, on a per kilo basis, are given to the most severely malnourished and the ration is reduced as the child progresses to recovery.

Thirdly, supply chain is simplified to a single RUTF and data management from 2 programs are merged into one. This streamlined programme should result in better coverage, a high proportion of children detected before MUAC\<115 mm, lower RUTF consumption per child and fewer acute malnutrition related hospitalisations.

Eligibility criteria: Inclusion Criteria:

* Be between 6 and 59 months old;
* Meet one of the acute malnutrition criteria defined as follows: PB \< 125mm or ratio Weight/Size (Z-score) \<-3 (WHO standard) or Oedema of grade +, ++;
* Be resident in the health area where the active screening session takes place;
* Have the free, informed and signed consent of the child's mother or guardian.

Exclusion Criteria:

* Children with medical complication or negative appetite test or oedema (grade +++)
* Children allergic to milk or peanuts;
* Children suffering from a known chronic pathology such as sickle cell anemia, trisomy 21, congenital heart disease, or neurological condition;
* Children currently in a malnutrition programme.

Primary outcomes:
measure: Success rate in each arm
timeFrame: 6 months after randomization
Secondary outcomes:
measure: Recovery rate in participants with severe acute malnutrition (WHO definition)
timeFrame: After RUTF treatment, through the 6 month study completion
Other outcomes:
measure: Consumption of RUTF
timeFrame: At the visit of recovery status occuring through the 6 month study completion
measure: Total weight gain and daily weight gain
timeFrame: At the visit of recovery status occuring through the 6 month study completion
measure: Total MUAC gain and daily MUAC gain
timeFrame: At the visit of recovery status occuring through the 6 month study completion
measure: Total length of RUTF treatment
timeFrame: At the visit of recovery status occuring through the 6 month study completion
measure: Absence of recovery
timeFrame: After 12 and after 16 weeks of nutritional follow-up
measure: Mortality
timeFrame: Through the 6 month study completion
measure: Hospitalisation
timeFrame: Through the 6 month study completion
measure: Relapse to a new episode of AM and to a new episode of SAM
timeFrame: During a 3 months period following the recovered episode of AM or of SAM at inclusion
Locations:
city: Kamuesha
country: Congo, The Democratic Republic of the
facility: Health Zone
state: Kasai
Study officials:
affiliation: Alliance for International Medical Action
name: SHEPHERD SUSAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: BECQUET RENAUD, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cazes C, Phelan K, Hubert V, Alitanou R, Boubacar H, Izie Bozama L, Tshibangu Sakubu G, Beuscart A, Yao C, Gabillard D, Kinda M, Augier A, Anglaret X, Shepherd S, Becquet R. Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a community-based individually randomised controlled trial in Kasai, Democratic Republic of Congo. BMJ Open. 2020 Dec 2;10(12):e041213. doi: 10.1136/bmjopen-2020-041213.
citation: Cazes C, Phelan K, Hubert V, Boubacar H, Bozama LI, Sakubu GT, Tshiala BK, Tusuku T, Alitanou R, Kouame A, Yao C, Gabillard D, Kinda M, Daures M, Augier A, Anglaret X, Shepherd S, Becquet R. Simplifying and optimising the management of uncomplicated acute malnutrition in children aged 6-59 months in the Democratic Republic of the Congo (OptiMA-DRC): a non-inferiority, randomised controlled trial. Lancet Glob Health. 2022 Apr;10(4):e510-e520. doi: 10.1016/S2214-109X(22)00041-9.
citation: Cazes C, Phelan K, Hubert V, Boubacar H, Bozama LI, Sakubu GT, Senge BB, Baya N, Alitanou R, Kouame A, Yao C, Gabillard D, Daures M, Augier A, Anglaret X, Kinda M, Shepherd S, Becquet R. Optimising the dosage of ready-to-use therapeutic food in children with uncomplicated severe acute malnutrition in the Democratic Republic of the Congo: a non-inferiority, randomised controlled trial. EClinicalMedicine. 2023 Feb 28;58:101878. doi: 10.1016/j.eclinm.2023.101878. eCollection 2023 Apr.