High-dose vitamin D3 in the treatment of complicated severe acute malnutrition in Pakistan: a double-blind randomised controlled trial (ViDiSAM)

We have previously shown that high-dose vitamin D3 improved weight gain and neurodevelopmental indices in children receiving standard therapy for uncomplicated severe acute malnutrition (SAM). We conducted a randomised placebo-controlled trial to determine whether two oral doses of 200,000 international units (IU) vitamin D3 would benefit children aged 6-59 months receiving standard therapy for complicated SAM in Lahore, Pakistan. The primary outcome was mean weight-for-height or -length z-score (WHZ) at 2-month follow-up. Secondary efficacy outcomes were mean WHZ at 6-month follow-up and mean lean mass index, Malawi Development Assessment Tool (MDAT) scores and serum 25-hydroxyvitamin D (25[OH]D) concentrations at 2- and 6-month follow-up. 259 children were randomised (128 to vitamin D, 131 to placebo), of whom 251 (96.9%) contributed data to analysis of the primary outcome. At 2-month follow-up, participants allocated to vitamin D had significantly higher mean serum 25(OH)D concentrations than those allocated to placebo (adjusted mean difference [aMD] 100.0 nmol/L, 95% confidence interval [CI] 72.2 to 127.8 nmol/L). This was not associated with an inter-arm difference in mean WHZ (aMD 0.02, 95% CI -0.20 to 0.23), or in any other anthropometric or neurodevelopmental outcome assessed at 2- or 6-month follow-up overall. However, sub-group analyses revealed some evidence of greater benefit from the intervention among participants with baseline serum 25(OH)D concentrations <50 nmol/L vs. ≥50 nmol/L for the outcomes of mean WHZ at 2-month follow-up (P for interaction 0.13) and mean MDAT score at 2-month follow-up (P for interaction 0.039). The intervention was safe. In conclusion, high-dose vitamin D3 elevated mean serum 25(OH)D concentrations in children receiving standard therapy for complicated SAM in Pakistan, but did not influence any anthropometric or neurodevelopmental outcome studied overall. Further trials are needed to determine whether children with lower baseline vitamin D status benefit from this intervention. The trial was registered at ClinicalTrials.gov with the identifier NCT04270643.