Impact of timing of RUTF dose reduction and visit frequency on acute malnutrition treatment effectiveness in Mali: A 2x2 Factorial Cluster-Randomized Controlled Trial

BackgroundSevere acute malnutrition (SAM) among children under 5 years of age is generally treated in outpatient settings providing caregivers with weekly ready-to-use therapeutic food (RUTF) rations to be administered at home. Recent updates to global treatment guidelines suggest that RUTF dose can be reduced once children progress to moderate stage (MAM). No evidence exists on the optimal timing of the dosage reduction or on ideal visit frequency. ObjectivesWe aimed to test the impact of 1) immediate RUTF dose reduction (1a) versus including a 2-week transition (1b) among children admitted with SAM and 2) fortnightly (2a) versus weekly (2b) visit frequency during MAM phase among children admitted with SAM and MAM. Methods and findingsThis prospective cluster-randomized controlled non-inferiority trial followed a 2 x 2 factorial design and divided 39 health areas (clusters) of Nara, Mali, into 4 groups implementing: A) 1a+2a B) 1a+2b, C) 1b+2a, and D) 1b+2b. Simplified, combined treatment was used providing 2 daily RUTF sachets to children admitted as SAM (mid-upper arm-circumference=MUAC<115mm or edema) and 1 daily RUTF sachet to children admitted with MAM (MUAC 115-124mm). Recovery was declared when a child reached MUAC [&ge;]125mm and absence of edema for 2 consecutive visits. Depending on the randomization arm, children admitted with SAM transitioned into receiving 1 daily RUTF sachet immediately upon reaching MUAC[&ge;]115mm (A+B) or after 3 consecutive visits (2 weeks) with MUAC[&ge;]115mm (C+D). Weekly visits were applied for all children with MUAC<115mm and then depending on randomization arm, visits continued weekly (A+C) or fortnightly (B+D) in the MAM phase. The main outcome was recovery and a non-inferiority margin of 10% was applied. Between April and December 2023, a total of 6249 children with MUAC<125mm or edema were admitted to treatment including 1451 children with SAM. On average 98% of children recovered with a mean duration of treatment of 6 weeks. Immediate transition resulted in non-inferior recovery compared to 2-week transition from SAM to MAM and no differences were observed in program outcomes (proportion of recovered, defaulted, non-recovered, transferred to inpatient care and deceased). However, we observed a non-significant trend of slight increase in the proportion of children regressing back to SAM after being MAM among children following immediate transition compared to those benefitting from 2-week transition. Fortnightly visit frequency in MAM phase resulted in non-inferior recovery compared to weekly visits throughout and no differences were observed in program outcomes. Duration of treatment was 2.5 weeks longer with fortnightly visits during MAM phase resulting in 23 sachets higher RUTF consumption compared to weekly visits throughout. ConclusionsWe recommend applying weekly visits throughout treatment where feasible for both children with MAM and SAM at admission and including a 2-week transition period before reducing the RUTF dose for children admitted with SAM once they reach MAM criteria. Trial registrationThe study was registered to clinicaltrials.gov (NCT06594341).