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Trial registered on ANZCTR


Registration number
ACTRN12618000264280p
Ethics application status
Submitted, not yet approved
Date submitted
5/01/2018
Date registered
20/02/2018
Date last updated
10/12/2018
Date data sharing statement initially provided
10/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
HAbIT Part 1: Incidence of new Human leucocyte antigen (HLA) Antibody formation after Transfusion with blood products in patients with end stage kidney disease who are planned for live donor kidney transplant: A prospective study
Scientific title
HAbIT Part 1: Incidence of De novo HLA Antibody formation after Transfusion with blood products in patients with end stage kidney disease who are planned for live donor kidney transplant: A prospective study

Secondary ID [1] 293717 0
Nil known
Universal Trial Number (UTN)
U1111-1207-2663
Trial acronym
HAbIT Part 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 306066 0
kidney disease 306373 0
Condition category
Condition code
Blood 305203 305203 0 0
Anaemia
Renal and Urogenital 305458 305458 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
HLA compatible red cell transfusion. This will be a personalised form of standard of care blood transfusion (as per Australian Patient Blood Management Guidelines), in which the blood donor will be selected to maximise HLA compatibility with the recipient. Selection will involve comparing the donor and recipient HLA types and choosing a donor who is matched as closely as possible with the recipient by HLA antigens and/or by epitope based methods. The red cells will also be irradiated, as is standard of care for red cell transfusions in some settings, but otherwise will not differ from standard of care red cell transfusion.
Intervention code [1] 299970 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304362 0
The primary outcome is the proportion of patients with de novo blood donor-specific HLA antibodies between 6 and 8 weeks following transfusion. Antibody positivity will be defined according to standard Australian Red Cross Blood Service Transplantation and Immunogenetics Services practice, and specificity determined with reference to blood donor HLA typing. An antibody positive in the post-transfusion sample but not the pre-transfusion sample will be considered de novo for the purposes of the study.
Timepoint [1] 304362 0
The timepoint for the primary outcome is visit 3, which can occur at any time between 6 and 8 weeks after the transfusion visit (visit 2).
Secondary outcome [1] 342500 0
Incidence of de novo non-DSA in participants receiving the intervention. De novo non-DSA will be defined as per de novo DSA, but where antibodies are not directed at donor epitopes. Antibody test results will be assessed by laboratory staff with expertise in HLA antibody test interpretation, who will be blinded to the status of participants.
Timepoint [1] 342500 0
The timepoint for this secondary outcome is visit 3, which can occur at any time between 6 and 8 weeks after the transfusion visit (visit 2).
Secondary outcome [2] 343607 0
Compatibility assessment- median HLA compatibility of supplied product by antigen (number of antigens mismatched) and eplet score.
Timepoint [2] 343607 0
Time of supply

Eligibility
Key inclusion criteria
5.2.1 Inclusion criteria
a) Eligible for blood transfusion according to local site clinical guidelines and anticipated to require a red cell transfusion on clinical grounds by participating unit
b) Patient assessed as competent to consent and participate
c) Transfusion must occur in a hospital setting (including satellite dialysis units)
d) Anticipated to be able to provide a further blood sample 6-8 weeks post-transfusion
e) CKD patient, ESKD patient, or other patient with renal disease, potentially eligible for live donor transplant as per local site transplant unit protocol
f) > 18 years of age
g) Not pregnant


Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Blood transfusion in 6 weeks prior to enrolment, or anticipated need for further transfusion in less than 6 weeks after the study transfusion event
b) Immunoglobulin therapy within 6 months prior to enrolment or scheduled within 4 weeks after enrolment (for treatments scheduled 6-8 weeks after enrolment the post-transfusion sample can be taken immediately prior to the treatment)
c) Severe illness that, in the opinion of the investigator, would compromise the ability of the subject to undergo further blood tests 6-8 weeks after transfusion
d) Pre-existing requirement for specific red cell product (eg directed donation)
e) Urgent transfusion (in the opinion of the investigator, delay in the transfusion for enrolment would compromise patient care)
f) Use of biologic medications targeting immune cells in 12 months prior to the trial (eg rituximab, bortezomib), or anticipated use of these medications in the 4 weeks post-transfusion (for treatments scheduled 6-8 weeks after enrolment the post-transfusion sample can be taken immediately prior to the treatment)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
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
Single group
Other design features
An observational substudy will examine the same endpoints in a more diverse group of patients (with and without chronic kidney disease) receiving standard of care red cell transfusions. This is considered a reference group to the intervention group rather than a formal control group, and will be registered as a separate study.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Statistical methods
95% confidence intervals for the primary outcome will be calculated using the binomial distribution (and normal approximation to the binomial distribution) for a range of “true” risks of de novo bDSA formation in the reference population. The same calculations will be performed for non-bDSA as a secondary endpoint. An exploratory multivariate analysis will be performed aiming to identify possible predictors of de novo bDSA and non-bDSA.

Sample size and power
A simple sample size calculation based on the binomial distribution was performed: 120 participants would yield a binomial probability of 6 or fewer positives in the intervention arm of p=0.04 if the risk from an unselected transfusion is 10% (ie 12 positives would be expected). As 10% is towards the lower end of estimates of background risk in the literature, the sample size of 120 is considered sufficient to detect a clinically significant benefit.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9687 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 18456 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 298335 0
Charities/Societies/Foundations
Name [1] 298335 0
Australian Red Cross Blood Service
Address [1] 298335 0
100-154 Batman Street
West Melbourne
VIC 3003
Country [1] 298335 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australian Red Cross Blood Service
Address
100-154 Batman Street
West Melbourne
VIC 3003
Country
Australia
Secondary sponsor category [1] 297450 0
Hospital
Name [1] 297450 0
Royal Melbourne Hospital
Address [1] 297450 0
Grattan Street
Parkville
VIC 3050
Country [1] 297450 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 299326 0
Australian Red Cross Blood Service HREC
Ethics committee address [1] 299326 0
Ethics committee country [1] 299326 0
Australia
Date submitted for ethics approval [1] 299326 0
29/01/2018
Approval date [1] 299326 0
Ethics approval number [1] 299326 0

Summary
Brief summary
The aim of the project is to evaluate the risk of antibodies to blood donor proteins developing after blood transfusions from blood donors selected to be compatible with the recipient. Participants will be patients who are planned to undergo a kidney transplant with a live donor. Testing for antibodies to donor proteins will be done before and 6-8 weeks after the transfusion to look for the development of new antibodies. This will help researchers to find a way to give patients blood transfusions without the risk of them developing antibodies that could put later transplants at risk.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80066 0
Dr Jeremy McComish
Address 80066 0
Australian Red Cross Blood Service
100-154 Batman Street
West Melbourne, VIC 3003
Country 80066 0
Australia
Phone 80066 0
+61 412 504 506
Fax 80066 0
+61 3 9694 3544
Email 80066 0
jmccomish@redcrossblood.org.au
Contact person for public queries
Name 80067 0
Dr Jeremy McComish
Address 80067 0
Australian Red Cross Blood Service
100-154 Batman Street
West Melbourne, VIC 3003
Country 80067 0
Australia
Phone 80067 0
+61 412 504 506
Fax 80067 0
+61 3 9694 3544
Email 80067 0
jmccomish@redcrossblood.org.au
Contact person for scientific queries
Name 80068 0
Dr Jeremy McComish
Address 80068 0
Australian Red Cross Blood Service
100-154 Batman Street
West Melbourne, VIC 3003
Country 80068 0
Australia
Phone 80068 0
+61 412 504 506
Fax 80068 0
+61 3 9694 3544
Email 80068 0
jmccomish@redcrossblood.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment

We would aim to make deidentified IPD available where possible but need to ensure that this is consistent with relevant state and federal legislation and participant informed consent.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable