Transfusion and Treatment of severe Anaemia in African Children: a randomised controlled trial (TRACT)
Lead Research Organisation:
Imperial College London
Department Name: Infectious Disease
Abstract
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, namely
1/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.
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, namely
1/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.
Technical Summary
TRACT is a multicentre randomised controlled trial to identify optimal transfusion strategies and supportive treatment for 3700 African children, aged 2 months to 12 years, presenting to hospital with severe anaemia (defined as haemoglobin (Hb) <6 g/dl). Children will be enrolled at admission to hospital over 2 years in Malawi and Uganda and followed for 6 months. The trial has been designed to address the poor outcome of this condition including high rates of in-hospital mortality, 6-month case fatality and chronic morbidity. Factors associated with poor outcome include potentially treatable co-morbidities such as recurrent infection and multiple vitamin deficiencies, which are not addressed in current guidelines. TRACT is designed to probe each of these multiple contributing factors directly. TRACT will simultaneously evaluate three ways to reduce short and longer-term mortality (primary endpoint) and morbidity following severe anaemia in Sub-Saharan Africa using a factorial design:
1/ Liberal transfusion (30ml/kg) versus conservative transfusion (20ml/kg) vs no transfusion (last strategy for children with Hb>4 g/dl and uncomplicated severe anaemia only)
2/ Multi-vitamin multi-mineral (MVMM) supplementation (including folate/iron) for 3 months versus routine care (folate/iron alone)
3/ cotrimoxazole prophylaxis for 3 months versus no antibiotic prophylaxis.
The primary outcome is cumulative mortality to 4 weeks (transfusion comparisons) and to 6 months for the nutritional support/antibiotic prophylaxis comparison. Secondary outcomes include mortality at 48 hours, 4 weeks, 3 months and 6 months (cumulative) (where not the primary outcome); development of new profound anaemia (Hb<4g/dl) during acute admission or development of severe anaemia (Hb<6g/dl) post discharge; readmission to hospital; proportion achieving correction of anaemia (defined by WHO as Hb>9g/dl); adverse events relating to transfusion.
1/ Liberal transfusion (30ml/kg) versus conservative transfusion (20ml/kg) vs no transfusion (last strategy for children with Hb>4 g/dl and uncomplicated severe anaemia only)
2/ Multi-vitamin multi-mineral (MVMM) supplementation (including folate/iron) for 3 months versus routine care (folate/iron alone)
3/ cotrimoxazole prophylaxis for 3 months versus no antibiotic prophylaxis.
The primary outcome is cumulative mortality to 4 weeks (transfusion comparisons) and to 6 months for the nutritional support/antibiotic prophylaxis comparison. Secondary outcomes include mortality at 48 hours, 4 weeks, 3 months and 6 months (cumulative) (where not the primary outcome); development of new profound anaemia (Hb<4g/dl) during acute admission or development of severe anaemia (Hb<6g/dl) post discharge; readmission to hospital; proportion achieving correction of anaemia (defined by WHO as Hb>9g/dl); adverse events relating to transfusion.
Planned Impact
Children with severe anaemia (SA) in Africa will be key beneficiaries. SA is a leading cause of morbidity, hospital admission and death in Sub-Saharan Africa, contributing to ~800,000 malaria deaths/year. Incomplete response to SA treatment results in relapse, readmission and death occurring soon after diagnosis. Current policies guiding clinical management are fragmented, based on weak evidence and often impractical. Since SA is so common the poor outcome and high 'hidden' chronic morbidity, if not adequately addressed, may be a key obstacle to achievement of Millennium Development Goal No.4 on child survival in Africa. The proposed trial will evaluate key elements of an integrated management strategy, including transfusion, in African hospitals on the basis of clinical effectiveness and costs.
In order for benefits to be realised, we plan to engage with (1) national policymakers (Ministry of Health, blood transfusion services, child health services); (2) international policymakers (WHO, UNICEF); (3) healthcare workers, nursing and paediatric associations, and NGOs involved in providing treatment or advocacy for children with severe anaemia in order to disseminate the outputs from the trial.
These stakeholders will benefit from our research, which aims to provide clear evidence on optimal treatment of children with severe anaemia, which is currently lacking. If the trial interventions reduce rates of re-admission to hospital, and are efficient and cost-effective for transfusion services, this could greatly improve overstretched acute child health and transfusion services.
In order to influence relevant policymakers and practitioners, we will also need to engage with academic audiences (who influence WHO policy), and those training health workers. Trainers of healthcare workers may benefit from new evidence from a controlled trial of what works and what does not work. Results from the trial may spur further research and academic debate, helping to catalyse further research on (cost-)effective interventions and improvement of care for children with severe anaemia in low-income settings.
Since the trial is large and pragmatic, incorporating children with both acute and acute-on-chronic anaemia, with few exclusion criteria, it will enable development of new guidelines and policy that cut across multiple 'syndromic' presentations - adopting a horizontal integrated rather than a vertical approach to management. Key enrolees will include children admitted to hospital with anaemia and malaria, sepsis, malnutrition, HIV, sickle cell disease and other conditions (eg lower respiratory tract infection). The pragmatic design is critical to translation of results to clinical practice; in malaria-endemic Africa, distinguishing between different underlying comorbidities, eg malaria and sepsis, in a severely ill child is often impossible at presentation to hospital. Since most treatment decisions are made on clinical criteria alone (or with limited diagnostic information eg malaria film and haemoglobin test), the trial results will have relevance to clinical practice and be immediately generalisable. There may be variation in response to the trial interventions and therefore the analysis plan will ensure that key syndromic groups, age groups and susceptibility (HIV or genetic factors) are considered. Whilst a single guideline is anticipated, refinement of this will be possible for particular sub-groups where response is not uniform.
The proposal will address whether the interventions represent value-for-money through a cost-effectiveness analysis (CEA) for each strategy investigated in the trial, which will draw upon existing knowledge and generate new costing data. Particular attention will be paid to blood transfusion service needs; ways in which blood can be delivered most efficiently to the benefit of the largest number of individuals (children in particular), will be explored during the trial and incorporated with trial results.
In order for benefits to be realised, we plan to engage with (1) national policymakers (Ministry of Health, blood transfusion services, child health services); (2) international policymakers (WHO, UNICEF); (3) healthcare workers, nursing and paediatric associations, and NGOs involved in providing treatment or advocacy for children with severe anaemia in order to disseminate the outputs from the trial.
These stakeholders will benefit from our research, which aims to provide clear evidence on optimal treatment of children with severe anaemia, which is currently lacking. If the trial interventions reduce rates of re-admission to hospital, and are efficient and cost-effective for transfusion services, this could greatly improve overstretched acute child health and transfusion services.
In order to influence relevant policymakers and practitioners, we will also need to engage with academic audiences (who influence WHO policy), and those training health workers. Trainers of healthcare workers may benefit from new evidence from a controlled trial of what works and what does not work. Results from the trial may spur further research and academic debate, helping to catalyse further research on (cost-)effective interventions and improvement of care for children with severe anaemia in low-income settings.
Since the trial is large and pragmatic, incorporating children with both acute and acute-on-chronic anaemia, with few exclusion criteria, it will enable development of new guidelines and policy that cut across multiple 'syndromic' presentations - adopting a horizontal integrated rather than a vertical approach to management. Key enrolees will include children admitted to hospital with anaemia and malaria, sepsis, malnutrition, HIV, sickle cell disease and other conditions (eg lower respiratory tract infection). The pragmatic design is critical to translation of results to clinical practice; in malaria-endemic Africa, distinguishing between different underlying comorbidities, eg malaria and sepsis, in a severely ill child is often impossible at presentation to hospital. Since most treatment decisions are made on clinical criteria alone (or with limited diagnostic information eg malaria film and haemoglobin test), the trial results will have relevance to clinical practice and be immediately generalisable. There may be variation in response to the trial interventions and therefore the analysis plan will ensure that key syndromic groups, age groups and susceptibility (HIV or genetic factors) are considered. Whilst a single guideline is anticipated, refinement of this will be possible for particular sub-groups where response is not uniform.
The proposal will address whether the interventions represent value-for-money through a cost-effectiveness analysis (CEA) for each strategy investigated in the trial, which will draw upon existing knowledge and generate new costing data. Particular attention will be paid to blood transfusion service needs; ways in which blood can be delivered most efficiently to the benefit of the largest number of individuals (children in particular), will be explored during the trial and incorporated with trial results.
Organisations
- Imperial College London (Lead Research Organisation)
- Cipla (Collaboration)
- Liverpool School of Tropical Medicine (Collaboration)
- Wellcome Trust (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- The Prince Charles Hospital (Collaboration)
- Mbale Regional Hospital (Collaboration)
- University of Amsterdam (Collaboration)
- Mbale Hospital (Collaboration)
- Radboud University Nijmegen (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- University of Malawi (Collaboration)
- Spectral Diagnostics Inc (Collaboration)
Publications
Nightingale H
(2016)
Validation of triple pass 24-hour dietary recall in Ugandan children by simultaneous weighed food assessment.
in BMC nutrition
Olupot-Olupot P
(2014)
Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.
in BMC medicine
Olupot-Olupot P
(2017)
High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Olupot-Olupot P
(2022)
A predictive algorithm for identifying children with sickle cell anemia among children admitted to hospital with severe anemia in Africa.
in American journal of hematology
Olupot-Olupot P
(2013)
Management of severe malaria: results from recent trials.
in Advances in experimental medicine and biology
Olupot-Olupot P
(2018)
Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda.
in Wellcome open research
Olupot-Olupot P
(2018)
Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda
in Wellcome Open Research
Sande L
(2017)
Abstracts of the 20th College of Medicine Research Dissemination Conference
in Malawi Medical Journal
Uyoga S
(2021)
Point-of-care haemoglobin testing in African hospitals: a neglected essential diagnostic test.
in British journal of haematology
Uyoga S
(2019)
Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub-Saharan Africa.
in Vox sanguinis
Guideline Title | Emergency Triage and Treatment of Children (RCPCH) |
Description | TRACT results influence ETAT recommendations for volume of blood to transfuse for children with severe anaemia |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical guidelines |
Impact | ETAT guidelines have been updated to recommend giving whole blood at 20ml/kg over 3 hours if the child's temperature is over 37.5 degrees C, or 30mls/kg if the temperature is 37.5 degrees C or below. This is based on the results of the TRACT trial. |
Description | WHO Severe malaria guidelines 2024 |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Severe malaria guidelines reviewed evidence from the Phase III FEAST trial (fluid bolus for shock) and TRACT trial (transfusion) The findings will be endorse in the new guidelines that are currently being developed and will include the new paediatric transfusion algorithm. |
Description | Major Overseas Programme Grant |
Amount | £45,000,000 (GBP) |
Funding ID | 203077/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2021 |
Description | Wellcome Collaborative Award in Science |
Amount | £3,944,185 (GBP) |
Funding ID | 209265/Z/17/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2018 |
End | 06/2022 |
Title | Development of Open Clinica for multisite trial |
Description | Open Clinica an open source database software that was specifically adapted for use in this trial by our programmer/data manager |
Type Of Material | Improvements to research infrastructure |
Provided To Others? | No |
Impact | Wider appreciation that open source software can be used as a platform for GCP trial and is compliant with FDA standards |
URL | http://www.ncbi.nlm.nih.gov/pubmed/21453454 |
Title | New methods for reliable evaluation of dietary intake |
Description | Quantitative assessment of daily food consumption by weighed food records followed by two independent assessments using triple pass 24-hour dietary recall on the following day. In conjunction with household measures and standard food sizes, volumes of liquid, dry rice, or play dough were used to aid portion size estimation. Inter-assessor agreement, and agreement with weighed food records was conducted primarily by Bland-Altman analysis and secondly by intraclass correlation coefficients and quartile cross-classification. RESULTS: 19 healthy children aged 6 months to 12 years were included in the study. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | The method was utilised in a sub-study of a large randomised controlled trial addressing treatment in severe childhood anaemia and formed the basis of a PhD |
URL | https://www.ncbi.nlm.nih.gov/pubmed/27795836 |
Title | Pragmatic Deferred Consent Proceedure for research in emergency medicine |
Description | FEAST is the largest Phase III paediatric fluid resuscitation trial ever undertaken. To ensure an ethical and humane process to approaching parents- we developed a novel strategy for deferred consent. We were uncomfortable with full consent waiver since this may mean that parents may never get to know that their child was involved in a research study - which if they had known at the time of admission they could have exercised their right to refuse. For the sickest children we opted for, and have ethical approval for, parental verbal assent, where parents understood that their child would be involved in a clinical trial, but the details would be given after recruitment - during informed consent- once their child was stablised. We plan substudies to evaluate this with social sciences groups specializing in research ethics. Our methodology has been written up and recently submitted for publication. |
Type Of Material | Improvements to research infrastructure |
Provided To Others? | No |
Impact | The ethical landscape has changed so vastly such that any pragmatic consenting process giving the key sensitivities to parents so they can weigh up risks and benefits contextually is now a rare phenomenon. Having presented the FEAST trial at international paediatric critical care conferences and more recently in a meningitis meeting - our consent process was welcomed as practical and helpful example by paediatricians who are struggling with European ICH GCP legislation. There have been two important regulatory developments in recent years. Firstly, in January 2007 EU paediatric medicine regulation (Regulation (EC) No 1901/2006) requiring all new license applications to include paediatric data. Followed by the December 2006 amendment to the EU trials directive that was intended to enable research in emergencies. Recent reports suggest this is not working in practice. The new requirement for research in children is compounded by the lack of guidance for conducting studies in this setting. FEAST trial consent process therefore sets a benchmark for future paediatric trials. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/23408950 |
Title | Additional file 2: of Validation of triple pass 24-hour dietary recall in Ugandan children by simultaneous weighed food assessment |
Description | Dataset for validation of triple pass 24-h dietary recall in Ugandan children by simultaneous weighed food assessment; Associated dataset in Excel format to enable validation of results and statistical interpretation. Gender has been removed to limit indirect identifiable information, but can be made available on request. (XLSX 26Â kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2016 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Validation_of_triple_pass_... |
Title | Additional file 2: of Validation of triple pass 24-hour dietary recall in Ugandan children by simultaneous weighed food assessment |
Description | Dataset for validation of triple pass 24-h dietary recall in Ugandan children by simultaneous weighed food assessment; Associated dataset in Excel format to enable validation of results and statistical interpretation. Gender has been removed to limit indirect identifiable information, but can be made available on request. (XLSX 26Â kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2016 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Validation_of_triple_pass_... |
Title | TRACT database |
Description | Open Clinica programmed for the transfusion trial |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Share facility for data entry in a multi centre trial |
Description | Human Genetics |
Organisation | Wellcome Trust |
Department | KEMRI-Wellcome Trust Research Programme |
Country | Kenya |
Sector | Academic/University |
PI Contribution | Basic science investigation for FEAST trial and planned investigation in TRACT trial. |
Collaborator Contribution | Design and conduct of basic science investigation linked to the clinical trial. |
Impact | Laboratory strengthening at Mbale Regional Referral Hospital, Eastern Uganda Multi-disciplinary: medical, immunology, molecular, genetics |
Start Year | 2011 |
Description | Mbale Clinical Research Institute, Mbale, Uganda |
Organisation | Mbale Clinical Research Institute |
Country | Uganda |
Sector | Hospitals |
PI Contribution | The Wellcome Trust has funded MCRI as part of the Major Overseas Award to Oxford-Kemri Wellcome Trust Programme. The collaboration is led by Programme members working with the Director of the Mbale Clinical Research Unit. We have established a strong relationship with MCRI having supported his PhD studies and his transition from a clinical and managerial career to a research career. |
Collaborator Contribution | Over the last 3 years Mbale has established a track record of clinical trials, receiving subcontracts for £996k and £812k in the last 3 years (subcontracted from the £3.2M and £2.4M awards for the TRACT and COAST trials) and recent award from MRC for a Phase II study of antibiotic treatment targeting non-typhoidal salmonellae (TABS). |
Impact | Award of a subcontract from the KEMRI Wellcome Trust Programme for £1.5 Million in 2016. The building of a new research laboratory to strengthen diagnostic and molecular research. The will enable the centre to expand its research portfolio in future. |
Start Year | 2016 |
Description | Mbale and Soroti Hospitals- Wellcome Trust Collaboration |
Organisation | Imperial College London |
Department | Faculty of Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | These previously research naïve hospitals were brought into the FEAST trial by the PI working in parntership with Malaria Consortium, Uganda. The site PIs have worked with the FEAST team to develop a clinical research platform to study acute malaria, which remains the major cause of admission. Comparative studies with Kilifi offer new potential insights into disease pathogenesis. |
Collaborator Contribution | Development of a clinical research team and undertaken a number of substudies A new laboratory will be built in the 2104, supported by Imperial College |
Impact | Routine clinical surveillance is due to be introduced and already a number of sub studies of life threatening childhood infections within FEAST have provided collaborative links with the KEMRI Wellcome Trust Programme. These include studies of pathogenesis (immunology and pathogen biology groups), evaluation of community perceptions of the consent process developed for FEAST, case control genetic studies and new biomarkers for severe malaria. A number of these studies are being conducted by the PI from Mbale who is registered on KEMRI Open University PhD programme. |
Start Year | 2008 |
Description | Mbale and Soroti Hospitals- Wellcome Trust Collaboration |
Organisation | Mbale Regional Hospital |
Country | Uganda |
Sector | Hospitals |
PI Contribution | These previously research naïve hospitals were brought into the FEAST trial by the PI working in parntership with Malaria Consortium, Uganda. The site PIs have worked with the FEAST team to develop a clinical research platform to study acute malaria, which remains the major cause of admission. Comparative studies with Kilifi offer new potential insights into disease pathogenesis. |
Collaborator Contribution | Development of a clinical research team and undertaken a number of substudies A new laboratory will be built in the 2104, supported by Imperial College |
Impact | Routine clinical surveillance is due to be introduced and already a number of sub studies of life threatening childhood infections within FEAST have provided collaborative links with the KEMRI Wellcome Trust Programme. These include studies of pathogenesis (immunology and pathogen biology groups), evaluation of community perceptions of the consent process developed for FEAST, case control genetic studies and new biomarkers for severe malaria. A number of these studies are being conducted by the PI from Mbale who is registered on KEMRI Open University PhD programme. |
Start Year | 2008 |
Description | Medical Research Council Clinical Trials Unit |
Organisation | Imperial College London |
Department | Department of Paediatrics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Work leading up the trials, identification of partners, trial sites and design and execution of clinical trials |
Collaborator Contribution | Design of clinical trials, trial governance and data management, statatistical expertise Multidisciplinary clinical trialists, infectious disease speacialists, health economists and specialists in health policy |
Impact | FEAST trial Publications Alexander Fleming Award TRACT trial |
Start Year | 2008 |
Description | Medical Research Council Clinical Trials Unit |
Organisation | Wellcome Trust |
Department | KEMRI-Wellcome Trust Research Programme |
Country | Kenya |
Sector | Academic/University |
PI Contribution | Work leading up the trials, identification of partners, trial sites and design and execution of clinical trials |
Collaborator Contribution | Design of clinical trials, trial governance and data management, statatistical expertise Multidisciplinary clinical trialists, infectious disease speacialists, health economists and specialists in health policy |
Impact | FEAST trial Publications Alexander Fleming Award TRACT trial |
Start Year | 2008 |
Description | POST and COAST trials |
Organisation | The Prince Charles Hospital |
Department | Social Work Department |
Country | Australia |
Sector | Hospitals |
PI Contribution | Development and conduct a pilot study (POST) for the main COAST trial |
Collaborator Contribution | Development of the pilot study (POST) and partnership with Fischer and Paykel |
Impact | none realised yet |
Start Year | 2012 |
Description | SMAART consortium |
Organisation | Wellcome Trust |
Department | Mahidol University-Oxford Tropical Medicine Research Programme |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The main aim of SMAART is to conduct better research studies faster, to improve outcomes from severe malaria. SMAART will act as the operational platform by which future research is planned in a coordinated and reciprocal manner to continuously update disease definitions and treatment guidelines for severe malaria. |
Collaborator Contribution | To overcome the barriers to achieving this goal, SMAART brings together applicants and co-investigators from three Wellcome Trust major overseas programmes (KEMRI Wellcome Trust Programme, Kenya, Malawi-Liverpool-Wellcome Trust Unit, Malawi (Prof David Lalloo) and Mahidol Oxford Research Unit, Thailand together with African scientists from existing or new collaborations and specialists in clinical trials ( MRC CTU at UCL) and ultimately national and international stakeholders. All are necessary to ensure that the most important questions are identified and combined optimally in the most efficient trial design which is acceptable and relevant to parents, healthcare professionals, ethical review boards and ministries of health. The network is thus a multi-disciplinary team providing complementary expertise and added value including links to other networks. The SMAART consortium encompasses decades of clinical and academic experience, track records of successful high quality research in low-income settings, and significant impact as evidenced by publication citation, grant funding and policy change. |
Impact | none yet; meeting planned for June 2016 to plan the grant submission to UK funder collaborative award |
Start Year | 2015 |
Description | SMAART consortium |
Organisation | Wellcome Trust |
Department | Malawi-Liverpool Wellcome Trust Clinical Research Programme |
Country | Malawi |
Sector | Academic/University |
PI Contribution | The main aim of SMAART is to conduct better research studies faster, to improve outcomes from severe malaria. SMAART will act as the operational platform by which future research is planned in a coordinated and reciprocal manner to continuously update disease definitions and treatment guidelines for severe malaria. |
Collaborator Contribution | To overcome the barriers to achieving this goal, SMAART brings together applicants and co-investigators from three Wellcome Trust major overseas programmes (KEMRI Wellcome Trust Programme, Kenya, Malawi-Liverpool-Wellcome Trust Unit, Malawi (Prof David Lalloo) and Mahidol Oxford Research Unit, Thailand together with African scientists from existing or new collaborations and specialists in clinical trials ( MRC CTU at UCL) and ultimately national and international stakeholders. All are necessary to ensure that the most important questions are identified and combined optimally in the most efficient trial design which is acceptable and relevant to parents, healthcare professionals, ethical review boards and ministries of health. The network is thus a multi-disciplinary team providing complementary expertise and added value including links to other networks. The SMAART consortium encompasses decades of clinical and academic experience, track records of successful high quality research in low-income settings, and significant impact as evidenced by publication citation, grant funding and policy change. |
Impact | none yet; meeting planned for June 2016 to plan the grant submission to UK funder collaborative award |
Start Year | 2015 |
Description | TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children |
Organisation | Liverpool School of Tropical Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design. |
Collaborator Contribution | Trial design Trial design |
Impact | Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011. The Trial was funded and the 6 papers have been published so far - highlighted in the TRACT grant |
Start Year | 2010 |
Description | TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children |
Organisation | University of Amsterdam |
Department | Department of Paediatrics |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design. |
Collaborator Contribution | Trial design Trial design |
Impact | Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011. The Trial was funded and the 6 papers have been published so far - highlighted in the TRACT grant |
Start Year | 2010 |
Description | TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children |
Organisation | University of Malawi |
Department | College of Medicine |
Country | Malawi |
Sector | Academic/University |
PI Contribution | Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design. |
Collaborator Contribution | Trial design Trial design |
Impact | Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011. The Trial was funded and the 6 papers have been published so far - highlighted in the TRACT grant |
Start Year | 2010 |
Description | Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) |
Organisation | Cipla |
Country | India |
Sector | Private |
PI Contribution | Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC |
Collaborator Contribution | Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics |
Impact | Submission to EDCTP- not funded Preparation of grant for 2013 |
Start Year | 2012 |
Description | Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) |
Organisation | Medical Research Council (MRC) |
Department | MRC Clinical Trials Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC |
Collaborator Contribution | Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics |
Impact | Submission to EDCTP- not funded Preparation of grant for 2013 |
Start Year | 2012 |
Description | Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) |
Organisation | Radboud University Nijmegen |
Department | Department of Pharmacology and Toxicology |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC |
Collaborator Contribution | Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics |
Impact | Submission to EDCTP- not funded Preparation of grant for 2013 |
Start Year | 2012 |
Description | Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) |
Organisation | Spectral Diagnostics Inc |
Country | Canada |
Sector | Private |
PI Contribution | Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC |
Collaborator Contribution | Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics |
Impact | Submission to EDCTP- not funded Preparation of grant for 2013 |
Start Year | 2012 |
Description | Uganda Blood Transfusion |
Organisation | Imperial College London |
Department | Department of Paediatrics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites |
Collaborator Contribution | Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial |
Impact | TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013 |
Start Year | 2013 |
Description | Uganda Blood Transfusion |
Organisation | Medical Research Council (MRC) |
Department | MRC Clinical Trials Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites |
Collaborator Contribution | Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial |
Impact | TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013 |
Start Year | 2013 |
Description | Uganda Blood Transfusion |
Organisation | Wellcome Trust |
Department | KEMRI-Wellcome Trust Research Programme |
Country | Kenya |
Sector | Academic/University |
PI Contribution | For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites |
Collaborator Contribution | Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial |
Impact | TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013 |
Start Year | 2013 |
Description | Uganda Blood Transfusion |
Organisation | Wellcome Trust |
Department | KEMRI-Wellcome Trust Research Programme |
Country | Kenya |
Sector | Academic/University |
PI Contribution | For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites |
Collaborator Contribution | Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial |
Impact | TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013 |
Start Year | 2013 |
Description | BBC World News Transfusion trial |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Increased awareness the children are the chief recipients of all donated blood in sub Saharan Africa- most give as emergency treatments Emphasized importance of research/clinical in the area of emergency treatment since most treatments given in the emergency room have not been tested in clinical trials Transfusion trial was designed to determine which children with severe anaemia would benefit from a blood transfusion (short and long-term) and which children did not require a transfusion (thus reducing the demand on the blood transfusion services |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.bbc.co.uk/news/world-africa-33925701 |
Description | ESPID Plenary Lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | I as invited and gave the plenary lecture at ESPID (European Society for Paediatric Infectious Diseases) which is an international conference addressing clinicians and policymakers. The talk ws well recieved to an audience of over 100 and which discussed the trials run from CTU, SHINE/CHAMP/SURE/STREAM/REALITY/CAPIT/ODYSSEY/ARROW Title of the talk: New ways of doing clinical trials in infectious diseases to maximise evidence generation |
Year(s) Of Engagement Activity | 2019 |
Description | Expert panel member for World Health Organisation technical consultation |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Following the release of a pre-print on point-of-care haemoglobin testing and engagement with an NGO called FIND, we were invited to share the results with a technical consultation to look at pre-qualification of point-of-care haemoglobin tests by the World Health Organisation. We then invited to stay and input into the discussions regarding the documents being drawn up to support pre-qualification. |
Year(s) Of Engagement Activity | 2023 |
Description | Giving the right amount of blood in transfusions can halve deaths among children with severe anaemia |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Results from the TRACT trial show that children with complicated severe anaemia (haemoglobin <4g/dl or 4-6g/dl with severity signs) who do not have a fever require larger volumes of blood transfusions than current World Health Organisation (WHO) guidelines recommend. However, for children admitted to hospital with a high temperature (fever), the amount recommended by guidelines is correct. Children who received the appropriate amount of blood, depending on whether they had fever or not, were at about half the risk of dying compared to those who received the other amount. These results were published yesterday in the New England Journal of Medicine. The TRACT trial also showed that children with uncomplicated severe anaemia (no severity signs, haemoglobin 4-6g/dl) do not require an immediate transfusion, as long as they are closely monitored for signs of complications, or their haemoglobin levels dropping, and receive a transfusion at that point. This suggests guidelines need to be updated to recommend different amounts of blood depending on whether a child has a fever. The trial also showed that very few children developed a transfusion reaction or a side effect such as heart failure or lung oedema, indicating that too much volume had been given. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.imperial.ac.uk/news/192330/larger-blood-transfusions-could-halve-deaths/ |
Description | Interviewed by Voice of America about NEJM Severe Malaria Perspective |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | New England Journal Perspective on Severe Malaria in African Children: need for continuing investment. I discussed the slow pace of progress in clinical trials in Africa; yet 10% of children with severe malaria will die. In the drive to eliminate malaria most scientists and policy makers felt that malaria was all but conquered. Many expressed surprise at the burden of disease. Thought published only on 22nd December 2016 the current Altmetrics for this article is 124. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.voanews.com/a/death-toll-from-malaria-among-african-children-called-unacceptably-high/366... |
Description | Meeting with Medicine Sans Frontiere Geneva - guideline review February 27th 2020 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Following the stakeholder meeting 11-12th February 2020 held in Kampala to which a representative from MSF (clinical guidelines) attended. The meeting in Geneva was organised to the clinical algorithm for management of severe anaemia implementing the TRACT trial results; endorsed by the conference, so that this can be discussed with all programme leads with the prospect of adoption of this into their updated paediatric guidelines. |
Year(s) Of Engagement Activity | 2020 |
Description | Participation in a webinar on anaemia for African Society of Blood Transfusion |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Work on whole blood vs red cell concentrates was presented at a public educational webinar hosted by African Society for Blood Transfusion societies on evaluation and management of anaemia in the context of Africa. |
Year(s) Of Engagement Activity | 2024 |
Description | RETRACT: REalising TRACT trial results: implications for African Blood Transfusion Services and policy makers |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | The blood transfusion results from TRACT have the potential to have major benefits in terms of improved outcomes for children with severe anaemia, and cost savings to blood transfusion services. In order for these benefits to be realised, we need to ensure that the results are shared with key stakeholders in sub-Saharan Africa, including national policymakers, Blood transfusion Services (BTS), health service providers and International policymakers. Together with the African Society of Blood Transfusion Services and Ugandan Paediatric Association Imperial College will co-host an international workshop, aimed at Blood Transfusion Services, and Paediatric Associations and policymakers, in sub-Saharan Africa to explore the findings and implications for implementing the relevant findings. We also request support to produce training films for teaching health workers and for piloting of the whole blood pedipacks (with the prospect of cost-savings to BTS). Since the meeting we have published one secondary analysis, a new transfusion algorithm and a commentary advocating for point of care haemoglobin testing |
Year(s) Of Engagement Activity | 2020 |
Description | TRACT 20mls vs 30mls animated abstract |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This animated abstract summarises the results of the TRACT trial in relation to the volume of blood children with severe anaemia require. |
Year(s) Of Engagement Activity | 2019 |
URL | https://vimeo.com/344562147 |
Description | TRACT algorithm briefing paper |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This briefing paper summarises recommendations and the clinical management algorithm developed at a stakeholder meeting held in 2020, based on the evidence from the TRACT trial. The consensus algorithm is designed to help health workers deliver evidence-based care to children with severe anaemia within the context of resource-limited settings. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.mrcctu.ucl.ac.uk/media/1972/tract-algorithm-briefing.pdf |
Description | TRACT briefing paper on 20mls vs 30mls transfusions |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | This briefing paper describes the results of the TRACT trial in relation to the volume required for blood transfusions for children with severe anaemia, and examines the implications for policy and practice. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.ctu.mrc.ac.uk/media/1709/tract-20vs30mls-briefing-final-020819.pdf |
Description | TRACT film |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This film explores the results and implications of the TRACT trial. |
Year(s) Of Engagement Activity | 2019 |
URL | https://vimeo.com/350115186 |
Description | TRACT immediate vs no immediate transfusion animated abstract |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This short animation summarises the results of the TRACT trial in relation to whether children with uncomplicated severe anaemia require an immediate transfusion. |
Year(s) Of Engagement Activity | 2019 |
URL | https://vimeo.com/344562242 |
Description | TRACT immediate vs no immediate transfusion briefing paper |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | This briefing paper describes the results of the TRACT trial in relation to immediate vs no immediate transfusion for children with uncomplicated severe anaemia, and examines the implications for policy and practice. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.ctu.mrc.ac.uk/media/1710/tract-immediate-vs-no-immediate-transfusion-briefing-final-0208... |
Description | TRACT immediate vs no immediate transfusion infographic |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This infographic summarises the results of the TRACT trial in terms of immediate vs no immediate transfusion for children with uncomplicated severe anaemia. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.ctu.mrc.ac.uk/media/1707/full-infographic-immediate-vs-no-immediate-transfusion-020819.p... |
Description | TRACT international stakeholders meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | We held a stakeholder meeting for paediatricians and blood transfusion services from across sub-Saharan Africa, to explore the implications of the TRACT trial for policy and practice. At the meeting we developed an algorithm for managing children with suspected severe anaemia. |
Year(s) Of Engagement Activity | 2020 |
Description | TRACT transfusion volume infographic |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This infographic summarises the results of the TRACT trial in relation to the volume of blood required for transfusion for children with severe anaemia. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.ctu.mrc.ac.uk/media/1708/full-infographic-transfusion-volume-020819.png |
Description | Talk at the International Blood Transfusion Society meeting in Cape Town (Nov 2023) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The talk presented a systematic review of point-of-care haemoglobin tests to an engaged audience who may use these tests for blood donation but also practitioners that use these tests to prescribe transfusions or not. A representative from the World Health Organisation was also there and engaged with the information to take back to policy making groups. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.isbtweb.org/events/isbt-cape-town-2023/programme-1.html |
Description | Training of new DMC members |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Finding new members with experience to populate Data Monitoring Committee is very hard. In Africa few statisticians involved in trials have been members of DMC. In the TRACT trial we have invited two junior statisticians to act as observers during DMC meetings - for training and experience none yet |
Year(s) Of Engagement Activity | 2014 |