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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Improved blood transfusion outcomes

Chronic blood transfusion

Condition category

Condition code

Blood

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]

Prevention

Intervention code [2]

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]

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]

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]

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]

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?

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

Recruitment in Australia

Recruitment state(s)

NSW,SA

Recruitment hospital [1]

Flinders Medical Centre - Bedford Park

Recruitment hospital [2]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [3]

Royal North Shore Hospital - St Leonards

Recruitment hospital [4]

Westmead Hospital - Westmead

Recruitment postcode(s) [1]

5042 - Bedford Park

Recruitment postcode(s) [2]

5000 - Adelaide

Recruitment postcode(s) [3]

2065 - St Leonards

Recruitment postcode(s) [4]

2145 - Westmead

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Australian Red Cross Blood Service

Address [1]

17 O'Riordan St
Alexandria
Sydney NSW 2015

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern Sydney Local Health District HREC

Ethics committee address [1]

Research Office
Kolling building, level 13
Reserve Road
Royal North Shore hospital
St Leonards NSW 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/05/2016

Approval date [1]

25/07/2016

Ethics approval number [1]

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

Dr Rena Hirani

Address

Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

rhirani@redcrossblood.org.au

Contact person for public queries

Name

Rena Hirani

Address

Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

rhirani@redcrossblood.org.au

Contact person for scientific queries

Name

Rena Hirani

Address

Research and Development
Australian Red Cross Blood Service
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

rhirani@redcrossblood.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

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