Transfusion and Treatment of severe Anaemia in African Children: a randomised controlled trial (TRACT)

非洲儿童严重贫血的输血和治疗：随机对照试验 (TRACT)

• 批准号: MR/J012483/1
• 负责人: Kathryn Maitland
• 金额: $ 415.95万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ012483%2F1
• 关键词: Transfusion; Treatment; severe; Anaemia; African

In sub-Saharan Africa severe anaemia is one of the most common reasons why children end up in hospital. It can kill children directly - and also contributes indirectly to the 800,000 child malaria deaths/year. For children hospitalised with severe anaemia (defined as a haemoglobin below 6g/dl) outcomes remain poor, with 9-10% dying in-hospital and an additional 12% dying in the 6 months following admission - and a further 6% having another episode of severe anaemia requiring additional treatment and re-hospitalisation. The high 6-month case fatality and chronic ongoing health issues of children with this condition indicate that the current recommendations and/ management strategies are not working in practice. Because severe anaemia is very common, the high 'hidden' sickness and mortality occurring after the initial diagnosis is likely to contribute to overall under-five mortality. If not adequately addressed, severe anaemia may therefore be an obstacle to achievement of the Millennium Development Goal No.4 on child survival in Africa. The investigators in this trial include specialists in child health, infectious diseases, transfusion medicine, and anaemia research. They have considerable experience in doing large clinical trials in hospitals with limited resources in Africa. Through extensive review of the available data and literature, the group have identified key areas of severe anaemia management which need to be addressed in a clinical trial, namely1/Which children should receive a transfusion? Current WHO guidelines, designed to avoid overuse of blood, recommend transfusions only in children with a haemoglobin (Hb) <4g/dl (or <6g/dl if accompanied by complications). These specific recommendations have not been evaluated in clinical trials and thus practice varies across African countries. We don't know if giving blood to all children with Hb <6g/dl would help. 2/ How much blood should be given in a transfusion? On current recommendations a quarter of children receiving transfusions remain severely anaemic and up to one third get two or more blood transfusions during a single hospital admission. We don't know if giving larger initial volumes of blood would help - this could also reduce risks from additional transfusion (which include bad blood matching or blood infections), and the amount of time health personnel spend getting blood ready. 3/ What, if any, longer-term support should children get after hospital admission? The major factors related to poor longer term outcome are multiple vitamin and mineral deficiencies and blood infections caused by bacteria - we don't know if giving vitamin supplements or antibiotics to prevent infections would improve outcomes. TRACT is designed to answer these questions. It is a randomised controlled trial involving 3700 children aged 2 months to 12 years admitted to hospitals with severe anaemia in Malawi and Uganda. The trial will take place over 2 years and children will be followed up for 6 months to make sure longer-term outcomes are captured. The trial will simultaneously look at three ways management of severe anaemia might be improved - with the aim of reducing early and late deaths, and anaemia recurrence or readmission to hospital. The trial will compare (i) current conservative WHO recommendations for transfusion against a more liberal approach, in terms of who gets blood and how much blood they get (iii) additional multi-vitamin multi-mineral supplements compared with the standard folate/iron recommended by WHO and (iii) an antibiotic, cotrimoxazole, to prevent new bacterial infections for 3 months compared with no antibiotic. The design is practical with broad, largely clinical inclusion criteria, so that children can be rapidly identified and recruited at hospital admission. The interventions are practical; many are already in use for other diseases so could be implemented in under-resourced paediatric health facilities across Africa at the end of the trial.

在撒哈拉以南非洲，严重贫血是儿童最终住院的最常见原因之一。它可以直接杀死儿童--也间接导致每年80万儿童死于疟疾。对于患有严重贫血(定义为血红蛋白低于6g/dl)住院的儿童，结局仍然很差，9-10%的儿童在住院期间死亡，另有12%的儿童在入院后6个月内死亡--另有6%的儿童患有另一次严重贫血，需要额外治疗和再次住院。患有这种疾病的儿童的6个月高病死率和长期持续的健康问题表明，目前的建议和/或管理战略在实践中并不奏效。由于严重贫血非常常见，在初步诊断后出现的高“隐性”疾病和死亡率可能会导致五岁以下儿童的总体死亡率。因此，如果得不到适当的解决，严重贫血可能成为实现关于非洲儿童生存的第四个千年发展目标的障碍。这项试验的研究人员包括儿童健康、传染病、输血医学和贫血研究方面的专家。他们在非洲资源有限的医院进行大型临床试验方面拥有相当丰富的经验。通过对现有数据和文献的广泛回顾，该小组确定了需要在临床试验中解决的严重贫血管理的关键领域，即哪些儿童应该接受输血？世卫组织目前的指导方针旨在避免过度使用血液，建议仅对血红蛋白为4g/dl(或如果伴有并发症，则为6g/dl)的儿童输血。这些具体建议尚未在临床试验中进行评估，因此非洲各国的做法各不相同。我们不知道给所有Hb&lt；6g/dl的儿童献血是否会有帮助。2/一次输血应该给多少血？根据目前的建议，四分之一接受输血的儿童仍然严重贫血，多达三分之一的儿童在一次住院期间接受了两次或两次以上的输血。我们不知道更大的初始输血量是否会有帮助--这也可以减少额外输血的风险(包括血液配型不佳或血液感染)，以及卫生人员花费在准备血液上的时间。3/如果有的话，儿童入院后应该得到什么更长期的支持？与长期预后不良相关的主要因素是多种维生素和矿物质缺乏以及细菌引起的血液感染--我们不知道服用维生素补充剂或抗生素预防感染是否会改善预后。Track就是为了回答这些问题而设计的。这是一项随机对照试验，涉及马拉维和乌干达患有严重贫血的医院收治的3700名2个月至12岁的儿童。这项试验将在两年内进行，并对儿童进行6个月的跟踪调查，以确保获得更长期的结果。这项试验将同时研究三种可能改善严重贫血管理的方法-目的是减少早期和晚期死亡，以及贫血复发或重新入院。这项试验将比较(I)世卫组织目前保守的输血建议与更自由的方法，在谁输血和他们输血数量方面；(Iii)与世卫组织推荐的标准叶酸/铁相比，额外的多维生素多矿物质补充剂；(Iii)抗生素，复方新诺明，与不使用抗生素相比，可在3个月内预防新的细菌感染。该设计是实用的，具有广泛的、主要的临床纳入标准，因此可以在入院时快速识别和招募儿童。这些干预措施是可行的；许多措施已经用于其他疾病，因此可以在试验结束时在非洲各地资源不足的儿科保健机构实施。

项目成果

Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial.

• DOI: 10.1016/s2214-109x(21)00565-9
• 发表时间: 2022-03
• 期刊: The Lancet. Global health
• 作者: George EC;Uyoga S;M'baya B;Kyeyune Byabazair D;Kiguli S;Olupot-Olupot P;Opoka RO;Chagaluka G;Alaroker F;Williams TN;Bates I;Mbanya D;Gibb DM;Walker AS;Maitland K;TRACT trial study group
• 通讯作者: TRACT trial study group

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data.

• DOI: 10.1186/s12889-021-11481-6
• 发表时间: 2021-07-29
• 期刊: BMC public health
• 影响因子: 4.5
• 作者: Connon R;George EC;Olupot-Olupot P;Kiguli S;Chagaluka G;Alaroker F;Opoka RO;Mpoya A;Walsh K;Engoru C;Nteziyaremye J;Mallewa M;Kennedy N;Nakuya M;Namayanja C;Nabawanuka E;Sennyondo T;Amorut D;Williams Musika C;Bates I;Boele van Hensbroek M;Evans JA;Uyoga S;Williams TN;Frost G;Gibb DM;Maitland K;Walker AS;TRACT trial group
• 通讯作者: TRACT trial group

Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review.

• DOI: 10.1186/1741-7015-12-31
• 发表时间: 2014-02-19
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Church J;Maitland K
• 通讯作者: Maitland K

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial.

• DOI: 10.1016/s2352-3026(15)00005-8
• 发表时间: 2015-03
• 期刊: The Lancet. Haematology
• 作者: Hassall OW;Thitiri J;Fegan G;Hamid F;Mwarumba S;Denje D;Wambua K;Mandaliya K;Maitland K;Bates I
• 通讯作者: Bates I

Additional file 1 of Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

乌干达和马拉维严重贫血儿童再入院的发生率和预测因素的附加文件 1：TRACT 试验数据的二次分析

• DOI: 10.6084/m9.figshare.15079799
• 发表时间: 2021
• 作者: Connon R