COMPLETED STUDY:

Research Details

TRACT Study

Full title

Transfusion and Treatment of Severe Anaemia in African Children

Study overview

Severe anaemia is a major cause of hospital admission and death among children in sub-Saharan Africa. It may result from malaria, bacterial infections, nutritional deficiencies, sickle cell disease and other inherited or acquired conditions.

Blood transfusion can be lifesaving, but blood supplies in many African hospitals are limited. At the time TRACT was designed, there was limited evidence to guide clinicians on which children required immediate transfusion, how much blood should be given and which treatments could improve recovery after discharge.

The TRACT Study evaluated several practical treatment strategies intended to reduce early deaths, hospital readmissions, recurrence of anaemia and longer-term illness.

Study objectives

The study aimed to:

  • Determine whether children with uncomplicated severe anaemia required immediate blood transfusion.
  • Compare higher and lower blood-transfusion volumes.
  • Evaluate whether multivitamin and multimineral supplementation improved recovery after discharge.
  • Determine whether cotrimoxazole prophylaxis reduced mortality and hospital readmission.
  • Assess the safety of the different transfusion and post-discharge strategies.
  • Examine haematological and nutritional recovery.
  • Assess the cost-effectiveness of the different treatment strategies.
  • Generate evidence to improve severe-anaemia treatment guidelines in African hospitals.

Study design

TRACT was a multicentre, open-label, Phase III randomised controlled trial. It used a factorial design that allowed several treatment questions to be evaluated simultaneously.

The study included three main randomised comparisons:

  1. Blood-transfusion timing and volume.
  2. Post-discharge nutritional supplementation.
  3. Post-discharge cotrimoxazole prophylaxis.

Participants were followed for six months after enrolment.

Study population

The trial enrolled children aged two months to 12 years who were admitted to hospital with severe anaemia, defined as a haemoglobin concentration below 6 g/dL.

Participants were divided into two clinical groups:

  • Complicated severe anaemia: Children with severe anaemia accompanied by serious clinical features that required immediate transfusion.
  • Uncomplicated severe anaemia: Children with haemoglobin between 4 and 6 g/dL who did not have signs of clinical severity.

A total of 3,199 children were enrolled between September 2014 and May 2017.

Study sites

The study was conducted at four hospitals in Uganda and Malawi:

  • Mbale Regional Referral Hospital, Uganda
  • Soroti Regional Referral Hospital, Uganda
  • Mulago Hospital, Kampala, Uganda
  • Queen Elizabeth Central Hospital, Blantyre, Malawi

The Mbale study team was led by Professor Peter Olupot-Olupot and worked closely with Mbale Regional Blood Bank and the wider TRACT research collaboration.

Transfusion interventions

Immediate transfusion versus clinical monitoring

Children with uncomplicated severe anaemia were randomly assigned to receive either:

  • An immediate blood transfusion; or
  • No immediate transfusion, with close clinical and haemoglobin monitoring.

Children in the monitoring group received a transfusion if their haemoglobin fell below 4 g/dL or if they developed signs of clinical severity.

Higher-volume versus lower-volume transfusion

Children allocated to immediate transfusion were also randomly assigned to receive either:

  • Lower-volume transfusion: 20 mL/kg of whole blood or 10 mL/kg of packed red cells.
  • Higher-volume transfusion: 30 mL/kg of whole blood or 15 mL/kg of packed red cells.

This comparison examined whether a larger initial transfusion would improve correction of anaemia, reduce repeat transfusions and lower mortality.

Post-discharge interventions

Nutritional supplementation

Children were randomly assigned to receive either:

  • Enhanced multivitamin and multimineral supplementation containing iron and folate; or
  • Standard iron and folate treatment.

The intervention was given for three months following hospital discharge. Children older than one year also received anti-helminthic treatment where appropriate.

Cotrimoxazole prophylaxis

Participants were also randomly assigned to receive either:

  • Daily cotrimoxazole prophylaxis for three months; or
  • No cotrimoxazole prophylaxis.

This comparison investigated whether preventing common bacterial and parasitic infections after discharge could reduce mortality and hospital readmission.

Study outcomes

The main outcomes included:

  • Mortality within 28 days
  • Mortality within six months
  • Haemoglobin recovery
  • Recurrence of severe anaemia
  • Requirement for additional transfusions
  • Length of hospital stay
  • Hospital readmission
  • Nutritional recovery
  • Infectious complications
  • Serious adverse events
  • Transfusion-related complications
  • Cost-effectiveness of the treatment strategies

Main findings

Timing of transfusion

Immediate transfusion did not significantly reduce 28-day or six-month mortality among children with uncomplicated severe anaemia compared with close monitoring and transfusion only when clinically indicated.

However, approximately half of the children initially managed without transfusion subsequently developed clinical severity or a further decline in haemoglobin and required transfusion.

The findings indicated that immediate transfusion can be safely avoided in some children with uncomplicated severe anaemia, provided that they are closely monitored and blood is readily available if their condition worsens.

Transfusion volume

Overall, there was no statistically significant difference in 28-day mortality between children who received 30 mL/kg and those who received 20 mL/kg of whole-blood equivalent.

However, an important difference was observed according to the child’s temperature at enrolment:

  • Among children without fever, the higher 30 mL/kg volume was associated with lower mortality.
  • Among children with fever, the higher volume was associated with increased mortality compared with 20 mL/kg.

These findings suggested that a single transfusion volume may not be appropriate for every child and that fever status should be considered when selecting the transfusion volume. Read the transfusion-volume results.

Nutritional supplementation

Enhanced multivitamin and multimineral supplementation did not improve six-month survival compared with standard iron and folate treatment.

Cotrimoxazole prophylaxis

Three months of cotrimoxazole prophylaxis did not significantly improve six-month survival compared with no prophylaxis.

The study nevertheless identified high levels of post-discharge illness and hospital readmission, demonstrating that children recovering from severe anaemia remain vulnerable after leaving hospital. Read the post-discharge treatment results.

Interpretation of the findings

TRACT demonstrated that children with uncomplicated severe anaemia do not always require an immediate transfusion. However, this approach depends on careful observation, repeated haemoglobin testing and rapid access to blood if the child’s condition deteriorates.

The trial also showed that transfusion volume should be individualised. Higher-volume transfusion may benefit children without fever but could be harmful to children who are febrile.

Neither enhanced nutritional supplementation nor routine cotrimoxazole prophylaxis improved survival, indicating that alternative interventions are required to reduce the high risk of illness and readmission after discharge.

Importance of the study

TRACT was one of the largest clinical trials examining childhood blood-transfusion practices in Africa. It provided high-quality evidence in an area where previous recommendations had largely been based on expert opinion and limited observational data.

The study’s findings are relevant to:

  • Paediatric transfusion guidelines
  • Emergency management of severe anaemia
  • Use of scarce blood supplies
  • Clinical monitoring of children not immediately transfused
  • Selection of appropriate transfusion volumes
  • Post-discharge care of vulnerable children
  • Prevention of avoidable deaths and hospital readmissions

A subsequent expert group used the findings to develop a practical consensus algorithm for managing severe anaemia in African children. Read the TRACT transfusion-management consensus.

Study leadership and collaborating institutions

The Chief Investigator was Professor Kathryn Maitland of Imperial College London and the KEMRI-Wellcome Trust Research Programme.

The Mbale site was led by Professor Peter Olupot-Olupot. Other site investigators included Professor Sarah Kiguli, Professor Robert Opoka, Dr Charles Engoru and investigators from Uganda and Malawi.

Major collaborating organisations included:

  • Imperial College London
  • MRC Clinical Trials Unit at University College London
  • KEMRI-Wellcome Trust Research Programme
  • Mbale Regional Referral Hospital
  • Makerere University and Mulago Hospital
  • Soroti Regional Referral Hospital
  • University of Malawi College of Medicine
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme
  • Uganda Blood Transfusion Service
  • Malawi Blood Transfusion Service
  • Mbale Regional Blood Bank
  • Liverpool School of Tropical Medicine
  • Amsterdam University Medical Centre

Sponsor and funding

The study was sponsored by Imperial College London.

It was funded by the UK Medical Research Council and the UK Department for International Development through their joint funding arrangements.

Ethical approval and consent

The study received ethical and regulatory approval from the relevant committees in the United Kingdom, Uganda and Malawi, including:

  • Imperial College Research Ethics Committee: ICREC_13_1_11
  • Makerere University School of Medicine Research and Ethics Committee: REC 2013-050
  • University of Malawi College of Medicine Research and Ethics Committee: P.03/13/1365
  • The Uganda National Counsil of Science of Technology
  • The Uganda National Drug Authority

Written informed consent was obtained from parents or legal guardians. An approved two-stage consent process was used for children presenting with life-threatening emergencies where delaying treatment could have placed them at further risk.

Trial registration

The TRACT Study was registered as:

ISRCTN84086586

The registration was approved on 11 February 2013.

Study status

The TRACT Study is completed. Participant recruitment ended in May 2017, and the principal trial results were published in 2019.

Key publications

Study Summary

  • TRACT Study – Transfusion and Treatment of Severe Anaemia in African Children

    The TRACT Study investigated optimal treatment strategies for children with severe anaemia in Uganda and Malawi. The Phase III trial enrolled 3,199 children at four hospitals, including Mbale Regional Referral Hospital. It evaluated when transfusions should be given, appropriate transfusion volumes, nutritional supplementation and cotrimoxazole after discharge. The study found that immediate transfusion could be safely avoided in some children with uncomplicated severe anaemia when close monitoring and rapid access to blood were available. It also showed that transfusion volume may need to consider fever status, while post-discharge supplementation and cotrimoxazole did not improve survival.

TRACT Closure Certificates Award Group Photo, September 2018

About

Ms. Adyango Catherine is a Human Resource Manager and Senior Grants Professional with over 15 years of experience in managing multimillion-dollar donor portfolios, project operations, and organizational systems strengthening. She currently serves as Human resource Manager at Mbale Clinical Research Institute (MCRI), where she leads in Human resource management,  donor compliance, project operations, and institutional capacity building.

At MCRI, Catherine has combined her expertise in grant management and human resources to establish efficient systems that support both research and staff welfare. She played a pivotal role in championing organizational culture reforms, developing HR policies, strengthening staff welfare schemes, and promoting inclusive recruitment processes. She also streamlined adoption of a Human Resource Management Information System (HRMIS/ESS), which reduced administrative bottlenecks and improved efficiency across teams.

Her academic background includes a Postgraduate Diploma in Human Resource Management (Uganda Management Institute), an MSc in Health Services Management, and a bachelor’s degree in business administration & management. Catherine is also pursuing ACCA training, demonstrating her commitment to continuous professional growth.

Catherine’s career reflects a strong commitment to strategic leadership, staff development, and inclusive programming, with a proven ability to balance donor expectations and human resource needs. Her work at MCRI has significantly contributed to building sustainable research capacity, enhancing compliance systems, and creating a supportive work environment that empowers both researchers and administrative staff.

About

Denis Amorut serves as the Study Site Coordinator at the Mbale Clinical Research Institute’s Soroti Site. He is a qualified Registered Nurse with a Bachelor of Science in Health Services Management from the Islamic University in Uganda and a Diploma in Comprehensive Nursing from Soroti School of Registered Comprehensive Nursing. Additionally, he is currently pursuing an Advanced Postgraduate Diploma in Clinical Research & Quality Assurance at James Lind Institute, showcasing his commitment to advancing his expertise in clinical research. Denis has an extensive professional background with 12 years in clinical nursing practice and 11 years dedicated to clinical research. He is registered with the Uganda Midwives and Nurses Council, highlighting his professional standing in the healthcare sector.
 
Throughout his career, Denis has held significant positions such as Trial Manager since November 2021 and previously as Study Site Coordinator at Soroti Regional Referral and Teaching Hospital from 2008 to October 2021. He also serves as a member of the Medicine and Therapeutic Committee at the same hospital since 2018. Denis has enriched his knowledge and skills through numerous online courses and certifications in areas like research ethics, data management for clinical studies, Good Clinical Practice (GCP), and managing health emergencies like Covid-19. His involvement in various research studies, including the TRACT study, and his roles in hospital committees further demonstrate his dedication to both practice and research in healthcare, focusing on improving patient care through evidence-based practices.

About

Ms. Linda Isabirye serves as the Public and Community Engagement Officer at MCRI, where her role encompasses a variety of tasks aimed at enhancing the Institute’s interaction with both internal and external communities. Her work is divided into two primary focuses: public engagement, where she communicates the Institute’s research and ideas to the public, and community engagement, where she assists others in conducting research and achieving their objectives.

In her community engagement efforts, Linda is involved in developing and sustaining a public engagement and involvement framework for the research program. She identifies local opportunities for community collaboration, nurturing relationships with MCRI’s research scientists, staff, and the broader community.

With over two years of experience, she has worked extensively with diverse community stakeholders. Her responsibilities include coordinating activities for the Community Advisory Board (CAB), designing, and overseeing the execution of Community Engagement (CE) initiatives. These initiatives are crucial for identifying, recruiting, and retaining volunteers, engaging community leadership, and supporting the formation and operation of community peer groups. This includes working with study participants, family support groups, and youth and adolescent groups, among others.

About

Rita Muhindo holds a MSc. Molecular Biology from Staffordshire University, UK. She attained her BSc. Biomedical Laboratory Science and Technology degree from Makerere University and an Advanced Diploma in Health Services Management from Islamic University in Uganda. She joined Mbale Clinical Research Institute in July 2011 as a laboratory technologist participating in setting up various laboratory assays for all clinical trials at the MCRI.

She is currently the laboratory manager of MCRI, a role which involves supervision all laboratory research activities at MCRI main and satellite laboratories. She has over twelve years of experience in managing laboratory clinical research and diagnostics service delivery across several key disciplines including molecular, immunology, hematology, microbiology and clinical chemistry.

She has keen interest in understanding the prevalence of red cell polymorphisms present in Ugandan donor populations. Her main focus of her MSc project was on the prevalence of Glucose-6-Phosphate dehydrogenase deficiency, α-thalassaemia and Haemoglobin S among Ugandan donors. Rita is also keen to explore the effects of these polymorphisms on the resolution of severe anaemia.

About

Dr. Charles Benard Okalebo is a highly qualified professional with a B. Pharm, an MPH, and currently a fellow in Infectious Disease and Field Epidemiology under the EDCTP-funded IDEA fellowship. His background as a pharmacist and public health specialist, combined with his role as a Quality Assurance Officer, has provided him with extensive experience in clinical research. This diverse training has honed his skills in assessing healthcare gaps, identifying problems, and designing projects to address these deficiencies. Dr. Okalebo values accuracy, integrity, quality, and career growth above all.
 
He is an experienced and determined professional in conducting clinical trials for both infectious and non-infectious diseases. With eight years in the research field, he has served as a Pharmacist and Quality Assurance Officer at the Mbale Clinical Research Institute, focusing on various types of clinical trials related to infectious diseases. His involvement spans across all phases of clinical trials (I-III), including protocol design, review, and implementation; navigating regulatory approval processes; managing investigational medicinal products (IMP); monitoring studies; establishing and implementing Quality Management processes; pharmacovigilance; and leading training sessions on the ethical conduct of research. The trials he has participated in include TRACT (ISRCTN84086586), GASTROSAM (ISRCTN76149273), PAC (ISRCTN11594437), FLACSAM (ISRCTN18051843), MIMBLE (ISRCTN10309022), and TABS (ISRCTN49726849) studies.
 
Dr. Okalebo is a dedicated researcher with a keen interest in advancing his career in pharmaco-epidemiology, statistics, and pharmacovigilance.

About

Felix Opio joined the Mbale Clinical Research Institute (MCRI) in April 2014 as Data Manager under the REACH (Realizing Effectiveness Across Continents with Hydroxyurea) ClinicalTrials.gov NCT01966731) which is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, long-term risks and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries (Mable Uganda,Kilifi Kenya, Luanda Angola and Kinshasa DRC).

He holds a Bachelor of Science in Computer Science from Gulu University, a post graduate diploma in Monitoring and Evaluation from Uganda Management Institute (UMI), Certificate in Project Management Professional from Devimpact Institute Kenya and various other certification in Clinical database development.

He Has 9 years of experience in Clinical Database design and Management, He is Currently overseeing data management work for the REACH study and all the day to day activities of the Project, He is also a member of the internal Clinical Trial Monitoring Unit and A chairperson Procurement Committee for Mbale Clinical Research Institute.

About

Ebitu Caleb Daniel serves as an I.T Support Officer at the Mbale Clinical Research Institute. He is recognized as an accomplished network and systems administrator, who takes pleasure in applying his skills to support and contribute to the technological advancement of research within the institution.
 
Ebitu graduated from Uganda Christian University Mukono with a Bachelor’s degree in Computer Science. Over the years, he has also acquired various certifications including CCNA, Information Security, Google Cloud Developer, PMP (Telecom), and Federated Identity Management.

About

Laban has accumulated over four years of experience in managing research financial processes since joining the Mbale Clinical Research Institute on July 1, 2019, as an Accounts Assistant. This experience complements his extensive background of over ten years in the banking sector, where he has previously worked for two banks in roles involving people management, cash management, internal controls, and accountability.

He holds a Bachelor’s degree in Business Studies, specializing in Accounting, from the Islamic University of Uganda. He is currently pursuing a Certificate of Public Accountants (CPA) from the Institute of Certified Public Accountants of Uganda (ICPAU), with only two papers remaining to complete the course.

Driven by an ambition to advance his career in accounting and expand his experience in research-related accounting managed by well-established systems and processes, he believes that MCRI is the ideal place for his professional growth.