Plain English Summary
Background and study aims
Some patients have blood disorders which mean they have very low numbers of platelets. Platelets are a type of blood cell important in preventing and stopping bleeding. Patients with very low numbers of platelets may need regular platelet transfusions. One problem with needing regular platelet transfusions is that some patients may develop an immune response against transfused platelets. The immune response is controlled by human leucocyte antigens (HLA), which are proteins found on the surface of transfused platelets. The body recognises the HLA as being different to their own and makes antibodies to attack them. These patients will need platelets specially matched so their body does not recognise the platelets as being different to their own and destroy them. The purpose of this study is to compare a new method against the current method of selecting platelets for patients who need specially matched platelets. The current method matches platelets by comparing the whole HLA. The new method will only look at a portion of the HLA, called the epitope, that is important in causing an immune response and this should provide an even closer match. To measure the success of the study platelet transfusions we will compare the rise in the patients platelet count after each study transfusion.
Who can participate?
Adults who have aplastic anaemia (low counts of red blood cells, white blood cells and platelets) or myelodysplatic syndrome (low counts of one ore more type of blood cell) and who need regular HLA matched platelet transfusions.
What does the study involve?
You will be asked to have some extra blood tests and complete a questionnaire. You will receive platelets when they are needed. The study will collect data on a maximum of 10 transfusions. Half of these transfusions will be matched using the standard method of HLA matching and half with be matched using the new epitope method.
What are the possible benefits and risks of participating?
The epitope method of matching platelets should provide a closer match than the standard HLA method which means the transfused platelets will be less likely to be destroyed by the body. There are no additional risks to you having platelet transfusions because the study platelets are the standard units given to patients. The only difference is that study platelets are selected to be a closer match.
Where is the study run from?
King's College Hospital London is the lead site for this study and other large hospitals in the London area and the south east of England will take part. We may also ask hospitals in other parts of England to take part.
When is the study starting and how long is it expected to run for?
October 2012 to May 2017
Who is funding the study?
NHS Blood and Transplant (UK)
Who is the main contact?
Ms Kay Harding
kay.harding@nhsbt.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Ms Emma Laing
ORCID ID
http://orcid.org/0000-0002-8309-0990
Contact details
NHS Blood and Transplant Clinical Trials Unit
Long Road
Cambridge
CB2 0PT
United Kingdom
-
Emma.Laing@nhsbt.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
13193
Study information
Scientific title
A comparison of HLA epitope-matched with standard HLA-matched platelet transfusions in raising the platelet count increment in alloimmunised thrombocytopenic patients with aplastic anaemia or low risk myelodysplastic syndrome: a double-blind randomised crossover superiority trial
Acronym
Study hypothesis
The current method of identifying HLA matched platelets for a patient is not always successful and the likelihood of finding a good donor match for patients with rarer HLA antibodies is low. Evidence from small retrospective studies suggests that matching platelets at the molecular (HLA epitope) level using a program called HLA MatchMaker gives a higher chance of a successful transfusion outcome. However, no studies have prospectively compared the effect of HLA epitope matched platelets on clinical bleeding outcomes and increase in platelet counts. Patients with aplastic anaemia or low risk myelodysplastic syndrome present and ideal group of patients as they frequently require platelet transfusions over a prolonged and often stable period, and often develop HLA antibodies.
This study has been designed to show no difference between how effective transfusion of HLA matched platelets and HLA epitope matched platelets are in increasing the patient platelet count. We predict that HLA epitope matched platelets will be more effective in increasing the patient platelet count. However, to ensure we are able to show that HLA epitope matched platelets do not give poorer platelet increments, we have used a non inferiority approach.
Ethics approval
NRES Committee London - Camberwell St Giles, 01/06/2012, ref: 12/LO/0695
Study design
Randomised trial
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Blood; Subtopic: Blood (all Subtopics); Disease: Non-malignant haematology
Intervention
Patients will receive one study platelet transfusion eight times, on eight separate occasions. Four of the platelet bags will be chosen using the standard method of HLA matching and four will be chosen using the HLAMatchmaker programme (epitope matched platelets).
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
The rise in platelet count after transfusion measured one hour after transfusion
Secondary outcome measures
1. Assessment of bleeding before and after platelet transfusion before transfusion and for 3 days after transfusion
2. Interval between platelet transfusions - The interval between the beginning of the trial transfusion until the next trial transfusion
3. Matched grade for standard HLA matched platelets
4. Number of epitope mismatches for epitope matched platelets
5. Reactions to trial platelets within 24 hours of transfusion
6. Rise in platelet count 24 hours after transfusion
7. Rise in platelet count after transfusion taking into account the platelet dose and patient body size at 1 and 24 hours
Overall trial start date
01/06/2012
Overall trial end date
31/05/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 16 years or older
2. Patients with aplastic anaemia or low-risk myelodysplastic syndrome
3. Patients who do not benefit from random (non-selected) donor platelet transfusions
4. Patients who require regular platelet transfusions according to local and British Committee for Standards in Haematology (BCSH) guidelines
5. Patients with evidence of HLA antibody(ies)
6. Patients that are expected to require multiple HLA selected prophylactic platelet transfusions
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 40; UK Sample Size: 40
Participant exclusion criteria
1. Patients with significant and palpable splenomegaly (enlargement of the spleen)
2. Patients who do not have serum HLA antibodies
3. Patients receiving anti-thymocyte globulin (ATG) treatment, specifically for the 5 days of ATG treatment and for the 14 days after ATG treatment. Once recovered from the treatment, the patient would be eligible to participate in the trial.
4. Patients who have previously participated in this study
5. Women who are pregnant or lactating
6. Patients unable to give written informed consent or comply with the protocol
Recruitment start date
01/06/2012
Recruitment end date
30/11/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrooke's Hospital
Hills Rd
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Hammersmith Hospital
Du Cane Rd
White City
London
W12 0HS
United Kingdom
Trial participating centre
King's College Hospital
Denmark Hill
Brixton
London
SE5 9RS
United Kingdom
Trial participating centre
Northampton General Hospital
Cliftonville
Northampton
NN1 5BD
United Kingdom
Trial participating centre
Nottingham City Hospital
Hucknall Rd
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Peterborough City Hospital
Edith Cavell Campus
Bretton Gate
Peterborough
PE3 9GZ
United Kingdom
Trial participating centre
Princess Royal University Hospital
Farnborough Common
Orpington
Kent
BR6 8ND
United Kingdom
Trial participating centre
Queen Alexandra Hospital
Southwick Hill Rd
Portsmouth
PO6 3LY
United Kingdom
Trial participating centre
Royal Bournemouth Hospital
Castle Ln E
Bournemouth
BH7 7DW
United Kingdom
Trial participating centre
Royal Free Hospital
Pond St
London
NW3 2QG
United Kingdom
Trial participating centre
Royal Hallamshire Hospital
Glossop Rd
Sheffield
S10 2JF
United Kingdom
Trial participating centre
St James's University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom
Trial participating centre
University College Hospital
235 Euston Rd
Fitzrovia
London
NW1 2BU
United Kingdom
Trial participating centre
University Hospital Lewisham
Lewisham High St
London
SE13 6LH
United Kingdom
Funders
Funder type
Government
Funder name
NHS Blood and Transplant
Alternative name(s)
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
31/05/2018
Participant level data
Not expected to be available
Basic results (scientific)
Publication list