Optimizing management of uncomplicated acute malnutrition in children in rural Niger: a 3-arm individually randomized, controlled, noninferiority trial

Abstract

Background: The Optimizing treatment for acute MAlnutrition (OptiMA) and Combined Protocol for Acute Malnutrition Study (ComPAS) strategies aim to simplify acute malnutrition treatment programs by treating severe and moderate cases with one product—ready-to-use therapeutic food (RUTF)—at gradually reduced doses. Objectives: This study aims to evaluate the noninferiority of treatment under OptiMA and ComPAS compared with Niger's standard protocol in children aged 6–59 mo included with 1) mid-upper arm circumference (MUAC) <125 mm or edema who achieved the primary outcome, defined as being alive, not acutely malnourished according to the inclusion criteria (MUAC ≥ 125 mm, weight-for-height z-score ≥−3, and no edema) and not having experienced an additional episode of acute malnutrition during a 6-mo period; 2) children with MUAC < 115 mm or edema who achieved nutritional recovery, defined as MUAC ≥ 125 mm and no edema for 2 wk; temperature <37.5°C; 4-wk minimum treatment. Methods: This individually randomized controlled trial (NCT04698070) was conducted in Niger 2021 to 2022. Children were assigned to either Standard, OptiMA, or ComPAS. Noninferiority, using 10% margin, was assessed in intention-to-treat (ITT) and per-protocol (PP) analyses. Results: For the primary outcome among 1732 children with acute malnutrition, noninferiority was demonstrated for ComPAS {51.9%, difference 1.0% [97.5% confidence interval (CI): –5.5%, +7.6%]} and OptiMA [49.7%, difference 3.2% (–3.3%, +9.9%)] in ITT analysis, but only for ComPAS in PP analysis. Among 1140 children with MUAC <115 mm or edema, standard protocol was superior in terms of nutritional recovery in ITT and PP analysis. There was no difference in mortality across the arms over 6 mo, and growth trajectories were similar between Standard and ComPAS, which used 50% less RUTF, but lower in OptiMA which used 32% less RUTF. A post-hoc analysis showed noninferiority of both intervention arms when 1-wk recovery was the defined endpoint, and 20% more missed visits in OptiMA and ComPAS. Conclusions: Only the ComPAS protocol demonstrated noninferiority to standard treatment in ITT and PP analyses for children with MUAC <125 mm or edema. The OptiMA protocol's lower performance is unclear, but it suggests that reduced RUTF dosage had limited influence on overall child growth, as ComPAS used less RUTF than OptiMA. For the most malnourished children with MUAC <115 mm or edema, the standard protocol showed a higher recovery proportion, primarily due to better attendance rather than differences in mortality or growth at 6 mo. Further studies are needed to better understand the acceptability and population-level impact of simplified protocols in multiple settings.