Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of paediatric admission in
Africa; post-discharge outcomes remain poor with high 6-month mortality (8%) and re-admission
(17%). This trial aimed to investigate pragmatic post-discharge interventions that might improve
outcomes.
Methods: Within the factorial open-label TRACT trial, Ugandan and Malawian children aged 2
months-12 years with severe anaemia (haemoglobin <6g/dl) at hospital admission were
randomised (using sequentially-numbered envelopes linked to a second set of non-sequentially
numbered allocations, stratified by centre and severity) to enhanced nutritional supplementation
with iron and folate-containing multi-vitamin multi-mineral supplements (MVMM) or iron/folate
at treatment doses (usual care), and to cotrimoxazole versus no cotrimoxazole, both given for 3
months post-discharge. Separately-reported randomisations investigated transfusion
management. The primary outcome was 180-day mortality analysed by intention-to-treat; followup was to 180-days (completed).
Findings: 3983 eligible children were randomised and followed for 180-days [164(4%) lost-tofollow-up]. Treatment was initiated in 1901(95%) MVMM, 1911(96%) iron/folate and 1922(96%)
cotrimoxazole. By day-180, 166(8%) MVMM vs 169(9%) iron/folate had died (hazard
ratio(HR)=0.97 (95% CI 0.79-1.21); p=0.81) and 172(9%) cotrimoxazole vs 163(8%) no
cotrimoxazole had died (HR=1.07 (95% CI 0.86-1.32); p=0.56). No evidence was seen of
interactions between these randomisations or with transfusion randomisations (p>0.2). By day180, 489(24%) MVMM vs 509(26%) iron/folate had experienced one or more SAEs (HR=0.95 (0.84-
1.07), p=0.40) and 500(25%) cotrimoxazole vs 498(25%) no cotrimoxazole (HR=1.01 (0.89,1.15)
p=0.85). Most SAEs were readmissions, occurring in 692(17%) children (175(4%) with ≥2 readmissions).
Interpretation: Neither enhanced supplementation with MVMM versus iron/folate treatment or
cotrimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest
that novel interventions are urgently required for severe anaemia, given the burden it places on
overstretched health services in Africa.