TY - JOUR
T1 - Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial
AU - Mpoya, Ayub
AU - Kiguli, Sarah
AU - Olupot-Olupot, Peter
AU - Opoka, Robert O.
AU - Engoru, Charles
AU - Mallewa, Macpherson
AU - Chimalizeni, Yami
AU - Kennedy, Neil
AU - Kyeyune, Dorothy
AU - Wabwire, Benjamin
AU - M'baya, Bridon
AU - Bates, Imelda
AU - Urban, Britta
AU - von Hensbroek, Michael Boele
AU - Heyderman, Robert
AU - Thomason, Margaret J.
AU - Uyoga, Sophie
AU - Williams, Thomas N.
AU - Gibb, Diana M.
AU - George, Elizabeth C.
AU - Walker, A. Sarah
AU - Maitland, Kathryn
PY - 2015/12/29
Y1 - 2015/12/29
N2 - BackgroundIn 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/DesignTRACT 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.DiscussionIf 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.Trial registrationCurrent Controlled Trials ISRCTN84086586, Approved 11 February 2013
AB - BackgroundIn 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/DesignTRACT 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.DiscussionIf 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.Trial registrationCurrent Controlled Trials ISRCTN84086586, Approved 11 February 2013
KW - Africa
KW - Anaemia
KW - Antibiotic prophylaxis
KW - Children
KW - Emergency medicine
KW - Haemoglobinopathies
KW - Malaria
KW - Micronutrients
KW - Sepsis
KW - Transfusion
U2 - 10.1186/s13063-015-1112-4
DO - 10.1186/s13063-015-1112-4
M3 - Article
SN - 1745-6215
VL - 16
JO - Trials
JF - Trials
IS - 1
M1 - 593
ER -
