Transfusion and treatment of severe anaemia in African children trial
| ISRCTN | ISRCTN84086586 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84086586 |
| Secondary identifying numbers | P39233, 203077/Z/16/Z |
- Submission date
- 25/01/2013
- Registration date
- 11/02/2013
- Last edited
- 14/02/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Haematological Disorders
Plain English Summary
Background and study aims
In sub-Saharan Africa severe anaemia in children is a leading cause of hospital admission, a major cause of direct mortality. Guidelines developed by the World Health Organization (WHO) encourage the rational use of blood transfusion to preserve this scarce resource and to reduce the risk of transfusion-transmitted infections. The evidence base for the paediatric guidelines is weak and thus adherence is poor. Outcome of severe anaemia is unsatisfactory with high rates of in-hospital (9-10%) and 6-month (12%) case fatality, and relapse or re-hospitalisation (6%), indicating that the current recommendations and management strategies are not working in practice. At the moment it is not known whether a blood transfusion is the best way to treat this and then how to treat or prevent the underlying illnesses, which may have caused the child to have severe anaemia.
The aim of this study is to:
1. Find out whether or not giving a blood transfusion is the best treatment. For children getting a blood transfusion we also do not know how much to give either the standard volume (dose) recommended in the current guidelines or a slightly higher volume (dose). We also want to find out whether or not giving extra treatments during the first three months after this hospital admission will prevent some of them from dying or becoming sick again. We will be looking at whether:
2. A multi vitamin multi mineral (MVMM) treatment called Sprinkles containing 15 different chemicals/vitamins is better than then usual recommended treatment of folate and iron.
3. Whether a single pill containing an antibiotic, cotrimoxazole, will fight infections and stop them from getting sick in the next 3 months.
Who can participate?
Children between the ages of 2 months to 12 years at the point of hospital admission. The blood test to check whether the child has anaemia is called a haemoglobin level. Children with a haemoglobin (Hb) less that 6g/dl will be included in the study.
What does the study involve?
Children will be treated according to standard Ministry of Health guidelines for severe illness and/or severe malaria.
1. Transfusion:
Children with a Hb below 4g/dl and those with Hb 4-6 g/dl with additional complications will all receive a transfusion. Half will receive the standard volume (dose) 20mg/kg of whole blood (as currently recommended) and the other half will receive a higher volume 30mg/kg.
Children with a Hb 4-6 g/dl haemoglobin without complications will be randomly allocated either receiving no transfusion (current WHO recommendations) or to receiving 20mg/kg of whole blood (as currently recommended) or 30mg/kg.
2. Vitamin treatments
Half the children will get iron and folate for 3 months (this is the current recommendation) while the other half will get a different MVMM medicine which is sprinkled onto their food every day for 3 months (or if the child is still breast feeding, mum will receive this medicine instead) to make the childs blood stronger.
3. Infection prevention
Often children with severe anaemia come back to hospital with another illness in the 6 months after this current admission. In order to try to prevent this, we will give half of the children a antibiotic tablet called cotrimoxazole for 3 months and the other half will not get this tablet. All children will have to come back after one month, three months and six months. We will check the health of your child at this visit, find out what food they have eaten on the day before they came to the clinic, find out whether they have been ill or to hospital since the last visit and check on whether they have been able to take the treatments and if they are causing any problem and then given them more treatments at the one month visit. When they come for these visits we will check on the strength of the blood (Hb level) and do a malaria test.
What are the possible benefits and risks of participating?
The direct benefits to the child and/or family include closer observation during the first 48 hours of admission, which, as a result, allows doctors and nurses to make important changes to the childs treatment during in-hospital admission, as well as being able to detect and treat any complications as they arise. All routine non-trial medications prescribed to treat the child will be made available. The parents or guardians for the children will be asked to return for follow up at the clinic 28, 90 and 180 days after admission. Reimbursement for transport cost after discharge and for follow up visits plus any treatment costs required during the visits will be made. Risks are minimal. Both MVMM and cotrimoxazole prophylaxis have been widely used in children with minimal risk. Although substantial efforts have been made to ensure the safety of blood, failure to correctly cross-match and/or infected blood have the potential to cause harm. The study will directly evaluate whether these potential risks are outweighed by improved survival. TRACT teams will work closely with the local blood transfusion services (BTS) to ensure that recommended safety and quality control practices are being maintained.
Where is the study run from?
The study is being run from KEMRI Wellcome Trust Programme, P.O Box 230-80108, Kilifi, Kenya. It is being conducted at three hospitals in Uganda (Mulago National Referral Hospital, Kampala Mbale and Soroti Regional Referral Hospitals, Eastern Uganda) and Queen Elizabeth Hospital, Blantyre, Malawi.
When is the study starting and how long is it expected to run for?
January 2013 to September 2017
Who is funding the study?
Medical Research Council and Department for International Development (UK)
Who is the main contact?
Professor Kathryn Maitland
k.maitland@imperial.ac.uk
Contact information
Scientific
KEMRI Wellcome Trust Programme
Kilifi
PO Box 230
Kenya
 ORCID ID |
0000-0002-0007-0645 |
|---|---|
| Phone | +254 (0)4175 22063 |
| k.maitland@imperial.ac.uk |
Study information
| Study design | Randomised controlled factorial trial with a 3x2x2 design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | TRansfusion and TReatment of severe Anaemia in African Children: a randomised controlled Trial |
| Study acronym | TRACT |
| Study hypothesis | 1. A liberal rather than a conservative blood transfusion policy will decrease mortality (cumulative to 4 weeks) in children admitted to hospital with severe anaemia (haemoglobin (Hb)<6g/dl). 2. Supplementary multi-vitamin multi-mineral treatments or cotrimoxazole prophylaxis or both for 3 months post discharge will reduce rates of readmission, severe anaemia relapse, re-transfusion or death (cumulative to 6 months) compared to current recommendations (iron and folate). |
| Ethics approval(s) | 1. Imperial College Research Ethics Committee (ICREC) 13/01/2011 2. Makerere University School of Medicine research ethics committee (SOMREC), 27/03/2013, #REC ref: 2013-050 3. University of Malawi College of Medicine research and ethics committee (COMREC), 08/08/2013, ref: P.03/13/1365 |
| Condition | Severe anaemia |
| Intervention | The trial will have a factorial design with 3 randomisations, each to address one of the potential approaches to reducing mortality and morbidity in children with SA: R1: Immediate liberal transfusion (30ml/kg) versus conservative transfusion (20ml/kg) versus no transfusion (last strategy only for children with uncomplicated SA and a Hb 4-6 g/dl). R2: Post-discharge multi-vitamin multi-mineral (MVMM) supplementation (which includes folate and iron) versus routine care (folate and iron) for 3 months. R3: Post-discharge cotrimoxazole prophylaxis versus no prophylaxis for 3 months. R1 addresses both conservative aspects of current guidelines: "whether to give" in uncomplicated SA (4-6g/dl without complications), and "how much to give" in all children with SA. The transfusion and post-discharge interventions (R2 and R3) will be open-label for reasons of practicality and compliance. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Cotrimoxazole, Nutrimix (Multivitamin Multimineral mix) 'Sprinkles' |
| Primary outcome measure | Cumulative mortality to 4 weeks for the transfusion strategy comparison, and to 6 months for the nutritional support/antibiotic prophylaxis comparison |
| Secondary outcome measures | 1. Mortality at 48 hours, 28 days, 90 day and 180 days (cumulative) (where not the primary outcome). 2. Morbidity: endpoints relating to the specific mechanisms of action of each intervention: 2.1. Re-admission to hospital 2.2. Proportion achieving correction of anaemia (defined by WHO as Hb>9g/dl) at 48 hours, 28 days, 90 day and 180 days 2.3. Development of new profound anaemia (Hb<4g/dl) during acute admission or development of severe anaemia (Hb<6g/dl) post discharge 3. Nutrition: changes in weight and MUAC at 90 day and 180 days 4. Anti-infection: changes in inflammatory markers (CRP, PCT), incidence of bacterial infections and malaria at 28 days, 90 day and 180 days |
| Overall study start date | 01/01/2013 |
| Overall study end date | 30/12/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 2 Months |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 3954 including at least 1950 complicated severe anaemia and no more than 2000 uncomplicated severe anaemia. |
| Total final enrolment | 1565 |
| Participant inclusion criteria | Children will be recruited at the point of hospital admission 1. Aged 2 months to 12 years 2. Severe anaemia (SA) (Hb<6g/dl) within 2h of admission to hospital 3. Carer willing/able to provide consent |
| Participant exclusion criteria | 1. Malignancy 2. Surgery 3. Acute trauma 4. Signs of bi-ventricular heart failure |
| Recruitment start date | 01/09/2014 |
| Recruitment end date | 14/05/2017 |
Locations
Countries of recruitment
- Malawi
- Uganda
Study participating centres
PO Box 7072
Makerere University
Kampala
-
Uganda
Pallisa Road Zone
PO Box 921
Mbale
-
Uganda
PO Box 289
Soroti
-
Uganda
Department of Paediatrics and Child Health
P/Bag 360
Chichiri
Blantyre
-
Malawi
Sponsor information
University/education
Joint Research Office
Sir Alexander Fleming Building
Imperial College
Exhibition Road
London
SW7 2AZ
England
United Kingdom
| Phone | +44 (0)20 7594 1188 |
|---|---|
| m.cranmer@imperial.ac.uk | |
| Website | http://http://www1.imperial.ac.uk/medicine/research/researchsupport/ |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Research council
No information available
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Wellcome, WT
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/09/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The trial results will be made available in a number of different formats and fora, in order to be appropriate for and accessible to different audiences. The trialists will use face-to-face meetings; workshops; open access peer-reviewed publication; policy briefs; presentation at international conferences; press releases; lay summaries; and websites. Depending on the results the trialists may also develop and distribute films and radio programmes; and will consult with members of the intended audiences to assess what other opportunities and tools for communicating they should use. |
| IPD sharing plan | The TRACT trial will follow a controlled access approach as per guidance from the MRC Methodology Hubs for Trials Methodology research (Tudor Smith et al, BMC Medicine 2016 PubMed ID 26675031). The ownership of the TRACT dataset will lie with the Trial Steering Committee (TSC), who will approve all requests for use of trial data before and after the trial ends (also to be approved by the TRACT Data Monitoring Committee before the trial ends). The dataset will be held electronically for at least 20 years after the end of the trial in accordance with local and MRC policies. The Data Sharing Policy will state that proposals to use TRACT data and samples will be welcomed, and supported widely where this does not conflict with existing plans within the trial team. Independent oversight of the data access process will be provided by TSC independent members and Imperial College, London (the trial sponsors). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 29/12/2015 | Yes | No | |
| Results article | results | 01/08/2019 | 01/08/2019 | Yes | No |
| Results article | results | 01/08/2019 | 01/08/2019 | Yes | No |
| Results article | results | 01/10/2019 | 23/09/2019 | Yes | No |
| Results article | Secondary analysis | 29/07/2021 | 02/08/2021 | Yes | No |
| Results article | 11/02/2022 | 14/02/2022 | Yes | No |
Editorial Notes
14/02/2022: Publication reference added.
02/08/2021: Publication reference added.
23/09/2020: Internal review.
23/09/2019: Publication reference added.
01/08/2019: Publication reference added.
01/08/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
25/10/2017: The overall trial end date was changed from 01/09/2017 to 30/12/2019.
24/10/2017: The recruitment end date was changed from 01/12/2016 to 14/05/2017.
14/07/2016: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/05/2013 to 01/01/2013.
2. The overall trial end date was changed from 30/11/2015 to 01/09/2017.
3. The recruitment start date was changed from 01/05/2013 to 01/09/2014.
4. The recruitment end date was changed from 30/11/2015 to 01/12/2016.
