Comparative effectiveness of lipid-nutrient spread supplementation regimens for moderate acute malnutrition in Ethiopia: The MODAM-MAM individually randomized controlled trial.

内容摘要

Moderate acute malnutrition (MAM), affecting over 30 million children globally, substantially increases the risk of morbidity and mortality. In 2023, the World Health Organization recommended lipid-based nutrient supplements (LNS) for children requiring supplementation for MAM, either ready-to-use supplementary food (RUSF) or ready-to-use therapeutic food (RUTF). However, evidence on the optimal product (RUTF or RUSF) and dosing strategy for children with MAM remains limited. The Modified Dosages for Acute Malnutrition MAM (MODAM-MAM) trial evaluated whether one- or two-sachet daily RUTF dosing were non-inferior to the de facto standard of one RUSF sachet daily for MAM supplementation. We conducted a three-arm, parallel, individually randomized controlled trial in Ethiopia. Children aged 6-59 months with MAM (mid-upper arm circumference (MUAC) 11.5-12.4 cm or WHZ between -3 and -2, without edema) were randomized to: one 540-kcal sachet of RUSF/day ("1-RUSF"), one 500-kcal sachet of RUTF/day ("1-RUTF"), or two sachets of RUTF/day ("2-RUTF"). Both intervention arms (1-RUTF and 2-RUTF) were evaluated for non-inferiority to the standard (1-RUSF) using a prespecified 6-percentage-point margin. The primary outcome was anthropometric recovery, defined as both MUAC ≥ 12.5 cm and WHZ ≥ -2 for two consecutive visits within 16 weeks. In total, 2,414 children were analyzed in the intention-to-treat analysis. Recovery proportions were 84.8% (679/801) for 1-RUSF, 85.0% (674/793) for 1-RUTF, and 88.1% (721/818) for 2-RUTF. Risk differences for recovery relative to the standard of care (1-RUSF) were +0.2 percentage points (95% CI [-3.3, 3.7]; p = 0.944) for 1-RUTF and +3.4 percentage points (95% CI [0.0, 6.7]; p = 0.050) for 2-RUTF, with both intervention arms meeting the non-inferiority criteria. Anthropometric gains and median length of stay (56 days) were similar across arms. Ration use was comparable for 1-RUSF and 1-RUTF, while 2-RUTF required 1.6-fold more product. Study limitations include evaluation of a single RUSF formulation and earlier-than-typical case-finding due to intensive screening. Both experimental arms, one RUTF sachet daily and two RUTF sachets daily, are non-inferior to the standard dosing of one RUSF sachet daily for MAM supplementation. Although two sachets of RUTF daily yielded slightly higher recovery, the marginal benefits do not justify substantially greater resource demands. Because one RUTF and one RUSF sachet daily yielded similar treatment outcomes, either product can be considered an effective option for supplementation. Product choice may therefore be guided by supply, cost, and operational considerations. clinicaltrials.gov NCT06056089.