Co-trimoxazole or multi-mineral multi-vitamins to improve post-discharge outcomes following severe anaemia in African children: a randomised controlled trial
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Published version
Supporting information
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-10
Date Acceptance
2019-07-18
ISSN
2214-109X
Publisher
Elsevier
Start Page
e1435
End Page
e1447
Journal / Book Title
The Lancet Global Health
Volume
7
Issue
10
Replaces
10044/1/73612
Copyright Statement
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council
Medical Research Council
Medical Research Council, UK
Imperial College Healthcare NHS Trust- BRC Funding
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S2214109X19303456?via%3Dihub
Grant Number
MR/J012483/1
MR/J012483/1
MR/J012483/1
MR/J012483/1
ICiC funding 2015/16
EP/S515875/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
DOUBLE-BLIND
IRON FORTIFICATION
YOUNG-CHILDREN
MALARIA
PROPHYLAXIS
MORTALITY
SPRINKLES
TRANSFUSION
DEFICIENCY
INFECTION
Anemia
Child
Dietary Supplements
Humans
Infant
Malawi
Patient Discharge
Trimethoprim, Sulfamethoxazole Drug Combination
Uganda
TRACT trial group
Humans
Anemia
Patient Discharge
Dietary Supplements
Child
Infant
Uganda
Malawi
Trimethoprim, Sulfamethoxazole Drug Combination
0605 Microbiology
1117 Public Health and Health Services
Publication Status
Published
Date Publish Online
2019-09-16