Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial

Kathryn Maitland*, Peter Olupot-Olupot, Sarah Kiguli, George Chagaluka, Florence Alaroker, Robert O. Opoka, Ayub Mpoya, Kevin Walsh, Charles Engoru, Julius Nteziyaremye, Machpherson Mallewa, Neil Kennedy, Margaret Nakuya, Cate Namayanja, Julianne Kayaga, Eva Nabawanuka, Tonny Sennyondo, Denis Aromut, Felistas Kumwenda, Cynthia Williams MusikaMargaret J. Thomason, Imelda Bates, Michael Boele von Hensbroek, Jennifer A. Evans, Sophie Uyoga, Thomas N. Williams, Gary Frost, Elizabeth C. George, Diana M. Gibb, A. Sarah Walker

*Corresponding author for this work

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Abstract

Background Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes. Methods Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete. Findings From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79–1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86–1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84–1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89–1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions). Interpretation Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole 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.
Original languageEnglish
Pages (from-to)e1435-e1447
JournalThe Lancet Global Health
Volume7
Issue number10
Early online date16 Sep 2019
DOIs
Publication statusPublished - 01 Oct 2019

ASJC Scopus subject areas

  • Medicine(all)

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    Maitland, K., Olupot-Olupot, P., Kiguli, S., Chagaluka, G., Alaroker, F., Opoka, R. O., Mpoya, A., Walsh, K., Engoru, C., Nteziyaremye, J., Mallewa, M., Kennedy, N., Nakuya, M., Namayanja, C., Kayaga, J., Nabawanuka, E., Sennyondo, T., Aromut, D., Kumwenda, F., ... Walker, A. S. (2019). Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial. The Lancet Global Health, 7(10), e1435-e1447. https://doi.org/10.1016/S2214-109X(19)30345-6