title: Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial.
abstract: BACKGROUND
  In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted.
  
  
  METHODS
  TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness.
  
  
  CONCLUSIONS
  If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. AMpoya@kemri-wellcome.org.
authors.forename: Ayub
authors.initials: A
authors.lastname: Mpoya
authors.affiliation: Department of Paediatrics, Mulago Hospital, Makerere University, PO Box 7072, Kampala, Uganda. skwalube@yahoo.co.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kiguli
authors.affiliation: Department of Paediatrics, Mbale Regional Referral Hospital Pallisa Road Zone, PO Box 921, Mbale, Uganda. polupotolupot@yahoo.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Olupot-Olupot
authors.affiliation: Department of Paediatrics, Mulago Hospital, Makerere University, PO Box 7072, Kampala, Uganda. opokabob@yahoo.com.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Opoka
authors.affiliation: Department of Paediatrics, Soroti Regional Referral Hospital, PO Box 289, Soroti, Uganda. charlesengoru@yahoo.co.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Engoru
authors.affiliation: College of Medicine, Department of Paediatrics and Child Health, University of Malawi, P/Bag 360, Chichiri, Blantyre 3, Malawi. mmallewa@mlw.medcol.mw.
authors.forename: Macpherson
authors.initials: M
authors.lastname: Mallewa
authors.affiliation: College of Medicine, Department of Paediatrics and Child Health, University of Malawi, P/Bag 360, Chichiri, Blantyre 3, Malawi. gaveta3@yahoo.com.
authors.forename: Yami
authors.initials: Y
authors.lastname: Chimalizeni
authors.affiliation: College of Medicine, Department of Paediatrics and Child Health, University of Malawi, P/Bag 360, Chichiri, Blantyre 3, Malawi. nkennedy@medcol.mw.
authors.forename: Neil
authors.initials: N
authors.lastname: Kennedy
authors.affiliation: Uganda Blood Transfusion Service, PO Box 1772, Kampala, Uganda. kyeyunedorothy@yahoo.com.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Kyeyune
authors.affiliation: Mbale Regional Blood Bank, PO Box 284, Mbale, Uganda. benjaminwabwire@yahoo.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wabwire
authors.affiliation: Malawi Blood Transfusion Service, PO Box 2681, Blantyre, Malawi. mbayab@yahoo.com.
authors.forename: Bridon
authors.initials: B
authors.lastname: M'baya
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi. Imelda.Bates@lstmed.ac.uk.|Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Imelda.Bates@lstmed.ac.uk.
authors.forename: Imelda
authors.initials: I
authors.lastname: Bates
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi. Britta.Urban@lstmed.ac.uk.|Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Britta.Urban@lstmed.ac.uk.
authors.forename: Britta
authors.initials: B
authors.lastname: Urban
authors.affiliation: Global Child Health Group, Emma Children's Hospital Academic Medical Centre, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. m.boele@amc.uva.nl.
authors.forename: Michael Boele
authors.initials: MB
authors.lastname: von Hensbroek
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi. r.heyderman@ucl.ac.uk.|Division of Infection and Immunity, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. r.heyderman@ucl.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Heyderman
authors.affiliation: MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. m.thomason@ucl.ac.uk.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Thomason
authors.affiliation: KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. suyoga@kemri-wellcome.org.
authors.forename: Sophie
authors.initials: S
authors.lastname: Uyoga
authors.affiliation: KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. tom.williams@imperial.ac.uk.|Wellcome Trust Centre for Clinical Tropical Medicine, Department of Paediatrics, Faculty of Medicine, St Marys Campus, Norfolk Place, Imperial College, London, W2 1PG, UK. tom.williams@imperial.ac.uk.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.affiliation: MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. Diana.gibb@ucl.ac.uk.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.affiliation: MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. elizabeth.george@ucl.ac.uk.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: George
authors.affiliation: MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. rmjlasw@ucl.ac.uk.
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.affiliation: KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. k.maitland@imperial.ac.uk.|Wellcome Trust Centre for Clinical Tropical Medicine, Department of Paediatrics, Faculty of Medicine, St Marys Campus, Norfolk Place, Imperial College, London, W2 1PG, UK. k.maitland@imperial.ac.uk.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
mesh_terms: D000367:Age Factors; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000871:Anthelmintics / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion / Q000401:mortality; D002648:Child; D046688:Child Mortality; D002675:Child, Preschool; D002985:Clinical Protocols; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D006304:Health Status; D006454:Hemoglobins / Q000378:metabolism; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D008295:Malawi; D009752:Nutritional Status; D010343:Patient Admission; D012008:Recurrence; D012107:Research Design; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D065227:Transfusion Reaction; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage; D014454:Uganda; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D006454:Hemoglobins; D014815:Vitamins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination