Condition category
Haematological Disorders
Date applied
25/01/2013
Date assigned
11/02/2013
Last edited
18/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 we do not know 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 your child to have severe anaemia.
Our aim 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?

We will invite children, between the ages of 2 months to 12 years, at the point of hospital admission to take part in a study. 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 child’s 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 child’s 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?
We aim to start the trial in May 2013. We will involve nearly 4000 children across three hospitals and will be recruiting over three years.

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Kathryn Maitland

ORCID ID

http://orcid.org/0000-0002-0007-0645

Contact details

KEMRI Wellcome Trust Programme
Kilifi
PO Box 230
Kenya
+254 (0)4175 22063
k.maitland@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

P39233

Study information

Scientific title

TRansfusion and TReatment of severe Anaemia in African Children: a randomised controlled Trial

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

1. Imperial College Research Ethics Committee (ICREC) 13/01/11
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

Study design

Randomised controlled factorial trial with a 3x2x2 design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Phase III

Drug names

Cotrimoxazole, Nutrimix (Multivitamin Multimineral mix) 'Sprinkles'

Primary outcome measures

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 trial start date

01/01/2013

Overall trial end date

01/09/2017

Reason abandoned

Eligibility

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 type

Patient

Age group

Child

Gender

Both

Target number of participants

3954 including at least 1950 complicated severe anaemia and no more than 2000 uncomplicated severe anaemia.

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

01/12/2016

Locations

Countries of recruitment

Malawi, Uganda

Trial participating centre

Mulago Hospital
Department of Paediatrics PO Box 7072 Makerere University
Kampala
-
Uganda

Trial participating centre

Mbale Regional Referral Hospital
Department of Paediatrics Pallisa Road Zone PO Box 921
Mbale
-
Uganda

Trial participating centre

Soroti Regional Referral Hospital
Department of Paediatrics PO Box 289
Soroti
-
Uganda

Trial participating centre

University of Malawi
College of Medicine Department of Paediatrics and Child Health P/Bag 360 Chichiri
Blantyre
-
Malawi

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

Joint Research Office
Sir Alexander Fleming Building
Imperial College
Exhibition Road
London
SW7 2AZ
United Kingdom
+44 (0)20 7594 1188
m.cranmer@imperial.ac.uk

Sponsor type

University/education

Website

http://http://www1.imperial.ac.uk/medicine/research/researchsupport/

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) and Department for International Development (through a concordat with MRC), United Kingdom Grant Number MR/J012483/1

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 our different audiences. We 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 we may also develop and distribute films and radio programmes; and will consult with members of our intended audiences to assess what other opportunities and tools for communicating we should use.

Intention to publish date

01/09/2018

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26715196

Publication citations

Additional files

Editorial Notes

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.