Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001093471
Ethics application status
Approved
Date submitted
5/08/2016
Date registered
12/08/2016
Date last updated
28/10/2021
Date data sharing statement initially provided
21/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Is extended blood group genotyping a better method to match patient and donor red blood cell donations in blood transfusion dependent patients?
Scientific title
Evaluating the benefits of extended blood group genotyping in transfusion dependent patients
Secondary ID [1] 289864 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Improved blood transfusion outcomes 299808 0
Chronic blood transfusion 299841 0
Condition category
Condition code
Blood 299736 299736 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Australian Red Cross Blood Service is supporting the study to evaluate the benefits of blood group genotyping in chronically transfused patient as a part of a routine transfusion laboratory protocol since this patient group is at greater risk of RBC antigen alloimmunisation. Since these patients form antibodies to red blood cell antigens this can cause laboratory staff to perform laborious and time consuming serological investigations. Performing red blood cell genotyping on these patients will enable better matching of donor units to patients which will potentially reduce the number of transfusions needed by the patient overall and should reduce the number of antibodies they form. To test this theory transfusion data and allo -antibody rates patients who are not receiving closely matched red blood cells units will used. To perform the genotyping, a single research blood sample will be obtained from a newly diagnosed haematology patient who is transfusion naive (or before their next transfusion if they are not transfusion naive but have only had up to 3 transfusions in the last 12 months). This blood sample will be taken at the same time as baseline samples are taken for standard of care requirements and will be 3mL in volume (1 teaspoon). Genomic DNA will be purified and blood group genotyping will be performed on the Australian Red Cross Blood Service HEA bead chip platform. No other blood samples will be used for the genotyping platform. Genotyping results will be provided to the researchers who can advise transfusion staff of which donor unit will be most suitable to transfuse into each patient. Hospital based transfusion laboratory staff will use this information to choose the most suitable unit prior to every transfusion received by that patient during the study period. The most suitable donor unit will be chosen on the closest available phenotype predicted by the genotype results. Donor units are phenotyped to at least 5 of the 39 red blood cell group systems. The decision to choose a unit will depend on how many blood systems each unit has had phenotyped and issued to that particular hospital. In some cases hospital transfusion laboratories can request certain phenotype units to be issued to them for a particular patient. This may be the case if patients are found to require more rare blood types.
All other information for this project on the rate of allo-antibody formation rates will be determined from the serum samples collected under routine hospital sample collections before each blood transfusion. The hospital laboratories will perform their own investigations on the serum from the patient to determine if antibodies have formed. This information will be provided to researchers via medical record data and will be used to compare with patients who had no genotyping performed prior to their blood transfusion. The data collection will be performed for each patient for up to 24 months and will vary depending on their individual treatment regimes.
Intervention code [1] 295549 0
Prevention
Intervention code [2] 295550 0
Early detection / Screening
Comparator / control treatment
Control patients will be recruited from Royal Adelaide Hospital. These patients will not be genotyped for red blood cell antigens prior to receiving their blood transfusion. These patients will get standard of care treatment with no intervention.
Control group
Active

Outcomes
Primary outcome [1] 299196 0
To determine if transfusion of genotype matched red blood cell units affects the mean number of blood transfusions required. This will be assessed by review of medical records for patients who do not have extended genotyping performed (data obtained from the Royal Adelaide Hospital) when compared with patients who are offered extended genotyping to match donor units more closely (patients enrolled at Flinders medical centre).
Timepoint [1] 299196 0
The number of transfusion required by patients who did or did not get genotype matched blood will be compared at the end of the study period (31/07/2021). The total number of transfusions for each participant will be assessed over 24 months of enrolment.
Secondary outcome [1] 326481 0
To determine if transfusion of genotype matched red blood cell units affects the mean number of allo-antibodies detected in each patients who did or did not get genotype matched blood. This will be assessed by review of medical records for patients who do not have extended genotyping performed (data obtained from the Royal Adelaide Hospital) when compared with patients who are offered extended genotyping to match donor units more closely (patients enrolled at Flinders medical centre).
Timepoint [1] 326481 0
A sample prior to the first blood transfusion will be taken to perform the genotype analysis. The number of allo-antibodies will be analysed by serological methods using standard care samples taken prior to every blood transfusion over the 24 month observation period for each participant.
Once serology testing has been performed the results will be provided to the researchers to compare with patients who did not have genotype analysis conducted.

Eligibility
Key inclusion criteria
Male and female patients over 18-80 years of age.
Patients with a haematological condition who require chronic RBC transfusions - it is hoped that as many patients as possible are transfusion naive for this study. where this is not possible patients who have had up to 3 blood transfusions within the last 12 months may also be recruited for analysis.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Minors under the age of 18 years
patients over 80 years of age
Mentally impaired or individuals in dependent relationships who are not sound of mind to consent to participate in this study

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A patients at Royal North Shore hospital and Flinders Medical Centre will consent to having blood group genotyping studies conducted. Data from patients at Royal Adelaide hospital will be used to determine if there are improvements on the rate of allo-immunisation to red blood cell antigens and the overall number of transfusion episodes required.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot study to determine if there is any potential for genotyped units to improve patient outcomes. Directed measures will be used including the number of transfusions required per patient and the number of antibodies formed. The number of patients to be recruited is 200. This recruitment target is achievable for the PhD student timeframe (PhD student is part-time). Since genotyping is also quite costly, the funding has been allocated to perform only a pilot study and this number of patients fits the funding model.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
2/04/2018
Actual
23/07/2017
Date of last participant enrolment
Anticipated
31/07/2020
Actual
2/10/2018
Date of last data collection
Anticipated
31/07/2021
Actual
2/10/2018
Sample size
Target
200
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 6426 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 6427 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 6428 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 10065 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 13968 0
5042 - Bedford Park
Recruitment postcode(s) [2] 13969 0
5000 - Adelaide
Recruitment postcode(s) [3] 13970 0
2065 - St Leonards
Recruitment postcode(s) [4] 21582 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 294242 0
Government body
Name [1] 294242 0
Australian Red Cross Blood Service
Country [1] 294242 0
Australia
Primary sponsor type
Government body
Name
Australian Red Cross Blood Service
Address
17 O'Riordan St
Alexandria
Sydney NSW 2015
Country
Australia
Secondary sponsor category [1] 293077 0
None
Name [1] 293077 0
Address [1] 293077 0
Country [1] 293077 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295666 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 295666 0
Research Office
Kolling building, level 13
Reserve Road
Royal North Shore hospital
St Leonards NSW 2065
Ethics committee country [1] 295666 0
Australia
Date submitted for ethics approval [1] 295666 0
09/05/2016
Approval date [1] 295666 0
25/07/2016
Ethics approval number [1] 295666 0
RESP/16/104

Summary
Brief summary
Chronically transfused patients receive multiple units of blood products over the course of their treatment. Multiple red blood cell (RBC) unit transfusions may lead to adverse transfusion related outcomes including the production of antibodies directed against RBC surface markers (antigens), haemolytic diseases and potential long-term donor cell survival, which is termed ‘microchimerism’.
Patients requiring transfusion are routinely typed for ABO and Rh (D) blood group antigens via serological methods since these antigens are immunogenic and its incompatibility with donor RBCs can lead to severe and fatal transfusion outcomes. Patients are also screened for the presence of clinically significant RBC antibodies that are either immunoglobulin (Ig) G or IgM isotypes. Antibodies against RBC antigens are either alloantibodies that are formed in response to foreign RBC antigens acquired during transfusion and pregnancy, or autoantibodies that are directed against an individual’s own RBC antigens observed in patients with haemolytic anaemias and autoimmune disorders.
Haemolytic anaemia is a condition where circulating immunoglobulins and/or complement bind to the surface of RBCs leading to their destruction. Direct antiglobulin testing (DAT) is used in clinical investigations to confirm and diagnose the cause of haemolytic anaemia. It detects the presence of IgG or various activated complement components attached to RBC surface membrane when haemolysis or haemolytic anaemia is present.
In patients diagnosed with haemolytic anaemia, a ‘pan-reactive’ autoantibody (antibodies indiscriminately reacting with all RBCs) coupled with a positive DAT result can cause difficulty in pre-transfusion testing, since the patient’s serum reacts to multiple donor RBC units. Furthermore, a strongly positive auto agglutinin may mask the presence of concurrent alloantibodies if present. The detection of patient alloantibodies via the auto- and allo- adsorption procedures are prolonged, labour intensive, complex and can often have no clear result. In these situations, a least incompatible but best matched donor RBC unit against the patient’s known phenotype becomes the only option available for transfusion.
This project will determine whether the use of RBC genotyping can be a useful integration into routine laboratory transfusion practice in Australia. Information on the patient’s blood group genotype can be used to predict the patient’s blood group phenotype and allow clinical staff managing chronically transfused patients to provide more appropriately matched donor RBC units. The ability to closely match a donor RBC unit to the patient could also prevent several rounds of manual serological laboratory investigations and reduce the risk of alloimmunisation in patients requiring long-term chronic transfusion regimes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68062 0
Dr Rena Hirani
Address 68062 0
Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015
Country 68062 0
Australia
Phone 68062 0
+61292342454
Fax 68062 0
+61292342411
Email 68062 0
[email protected]
Contact person for public queries
Name 68063 0
Dr Rena Hirani
Address 68063 0
Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015
Country 68063 0
Australia
Phone 68063 0
+61292342454
Fax 68063 0
+61292342411
Email 68063 0
[email protected]
Contact person for scientific queries
Name 68064 0
Dr Rena Hirani
Address 68064 0
Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015
Country 68064 0
Australia
Phone 68064 0
+61292342454
Fax 68064 0
+61292342411
Email 68064 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
this was not part of our ethics consent form signed by the participants, therefore we cannot provide ethically provide individuals data/results. we will provide aggregated data via request after the results are publicly available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.