Acute Malnutrition in Infancy (Disorder) Clinical Trial
Official title:
Evaluation of Two Optimizing and Simplifying Strategies on Acute Malnutrition Treatment in Children Aged 6 to 59 Months in Mirriah District, Zinder, Niger
Acute malnutrition (AM) is a continuum condition, arbitrarily divided into severe and moderate categories (SAM, MAM) which are managed separately, with programs overseen by different agencies with different products and supply chains. Such separation complicates delivery of care, contributes to poor program performance, and creates confusion among caregivers. Reduction in the mortality burden from AM will stem from improved simplicity, efficiency and cost-effectiveness of current protocols. Eligibility for SAM treatment in the current Niger protocol is complex. It is determined by 3 independent criteria: nutritional oedema, Mid-Upper Arm Circumference (MUAC) < 115 mm or weight-height Z score (WHZ) <-3. Also, the Ready to Use Therapeutic Food (RUTF) ration in Niger protocol (130-200 kcal/kg/d) is paradoxical. The amount of RUTF prescribed in the first weeks of treatment is often less than what given to child reaching recovery (MUAC > 125 and WHZ >-2), because weekly ration is determined by the child's weight. Rate of weight gain is highest in the first two weeks of treatment, then plateaus - suggesting no benefit of increased RUTF ration at the end of treatment. Progressive reduction is a more rational use of RUTF and this supplement is equally effective for SAM and MAM. This community-based non-inferiority trial will compare two strategies for the treatment of AM to the Niger protocol for SAM and MAM. The Optimizing treatment for acute MAlnutrition (OptiMA) strategy uses MUAC < 125 mm or nutritional oedema as admission criteria and optimizes RUTF by adapting doses to the degree of malnutrition. RUTF dose for MUAC < 115 mm or oedema is 170 kcal/kg/d and progressively reduces to 75 kcal/kg/d as MUAC increases. The Combined Protocol for Acute Malnutrition Study (ComPAS) uses the same eligibility criteria like OptiMA, but simplifies more the RUTF ration by providing 1000 kcal/d for children with oedema or MUAC < 115 mm and 500 kg/d for children with MUAC 115-124 mm. Children are considered recovered if they have 2 consecutive weekly MUAC measures ≥ 125 mm. Children will be individually randomized to treatment in one of the 3 study arms and will attend clinic visits weekly until nutritional recovery. After discharged, they will be monitored monthly via a nurse-conducted home visits until 6 months post-inclusion. The trial arms will be compared using a composite outcome indicator that includes vital status, anthropometric measures and relapse following the index AM episode. The hypothesis is that simplified strategies could substantially increase the number of children in care compared to current SAM programs without requiring additional RUTF or staffing while maintaining recovery rates in line with current programs.
The main outcome, the success rate, is defined by a composite of three endpoints : alive, not acutely malnourished per the definition applied at inclusion and not having an additional episode of AM throughout the 6- month observation period. All other children are classified as 'unsuccessful'. The secondary major outcome, the recovery rate, is defined by reaching during the 6 month follow-up a MUAC>=125 and no oedema during two consecutive weeks, a minimum RUTF treatment period of 4 weeks and good clinical condition. Sample size: For the main objective, the expected success rate is 68% with a statistical power of 90%. For the secondary priority objective n°1, the expected recovery rate is 82% and for the secondary priority objective n°2, the expected recovery rate is 74% with a statistical power of 80%. For all objectives, the margin of non-inferiority set is 10% with a level of significance set at 1.25% unilaterally. An inflation of 5% to account for unexploitable data was also added. The number of randomized subjects required is: - 568 participants to meet the main objective; - 295 participants with severe acute malnutrition to meet the secondary priority objective n°1. - 384 participants with MUAC<115mm at admission to meet the secondary priority objective n°2. Data collection and monitoring : A paper form will be completed by the trial nurses during the outpatient follow-up or at home visits. Data will be recorded by data entry agents supervised by a data manager using RedCAP software. Data monitoring will be performed every week at each site by clinical trial monitors under the responsibility of the research activities manager, according to the recommendations of Good Clinical Practices. All data entered in the database will be checked for completeness and consistency. The methods of data entry, coding, control, validation and database freezing will be described in a "data management" guide. Before the implementation of the trial, a monitoring plan will be established. Analysis : Before the end of the inclusion period, a statistical analysis plan will be established. The occurrence of the primary endpoint (success rate) will be compared between the OptiMA and ComPAS strategies to the standard protocol. The occurrence of the primary secondary endpoint (recovery rate) will be compared between the OptiMA and ComPAS strategies to the standard protocol, for children randomized in the severe acute malnourished stratum and for children admitted with a MUAC<115mm. These comparisons will be made by Intention To Treat (ITT) (including all randomized participants), and Per-Protocol (PP) (including only those participants who received the full randomized treatment strategy). The primary analysis (success in the overall population regardless of the level of malnutrition) and the main secondary analysis (recovery rate in the "severely malnourished" stratum) in ITT and PP are non-inferiority analyses. The OptiMA and ComPAS strategies will be deemed non-inferior to the standard strategy if the primary and main secondary analysis statistically demonstrate non-inferiority in both ITT and PP. The primary analyses in terms of success and recovery will be performed on available data. In case of missing data, a sensitivity analysis will be performed using the maximum bias method. Missing data can be vital status if the child is absent at the last visit, and anthropometric data (weight, MUAC, height). In the case of missing height data, the last available height can be taken into consideration given the low variability of this value from one month to the next. The probabilities of success, recovery and relapse in each of the strategies and the quantities of RUTF consumed per child to achieve recovery will serve to construct a cost-effectiveness model. ;