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Trial registered on ANZCTR


Registration number
ACTRN12618001459213
Ethics application status
Approved
Date submitted
9/04/2018
Date registered
30/08/2018
Date last updated
2/08/2019
Date data sharing statement initially provided
2/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Giving patients back the blood that they lose during surgery: Does this impact their immune system?
Scientific title
Does transfusion-related immune modulation occur following intraoperative cell salvage: A pilot study
Secondary ID [1] 294500 0
no secondary ID
Universal Trial Number (UTN)
U1111-1211-8083
Trial acronym
TRIMICS (Transfusion Related Immune Modulation during Intraoperative Cell Salvage)
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Immune modulation after blood transfusion 307273 0
Condition category
Condition code
Inflammatory and Immune System 306391 306391 0 0
Other inflammatory or immune system disorders
Blood 306392 306392 0 0
Other blood disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Blood samples will be collected from 20 participants by clinicians (trained and experienced in phlebotomy) at the Royal Brisbane and Women’s Hospital and analysed at the Red Cross Blood service through a panel of tests/assays to evaluate the immune response related to blood transfusion and cell salvage.

This is the first time a prospective analysis of the cell salvage product and patient immune response has been carried out. The study protocol, logistics etc. are all required to be established. This study will recruit 20 patients as a pilot.

In view of the fact that the study is novel, there is no published data available where the full panel of assays proposed were used to test and compare allogeneic blood transfusion and intraoperative cell salvage responses. Therefore there is no comparable (published) data to base an accurate power analysis and sample size on.

Intended samples:
1) Before surgery (patient sample), (Sample 1)
2) After cell salvage processing (product sample), (Sample 2)
3) After cell salvage filtering (product sample), (Sample 3)
4) Immediately after surgery (patient sample), and (Sample 4)
5) At day 3 after surgery (patient sample). (Sample 5)

“TRIM is a complex inflammatory process” and the lack of diagnostic criteria make it difficult to define. It is best to consider the proposed project as a project of three parts.
The first part of the study: Samples 2 and 3 will be used to characterise the cell salvage product at different stages of its production by using established panels at the blood service.
The second part of the study: Samples 1, 4 and 5 will be used to assess ABT and ICS immune response using established assays at the blood service. Specifically the immune response will be assessed in an in vitro assay. In addition to direct assessment of the patient responses, we had added a transfusion assay where we will mix the admission sample with allogeneic (routine collected and stored blood at the blood service) to see whether there is a difference in immune profile following exposure to cell salvaged vs. allogeneic blood.

Samples 1 and 4 will be taken by the anaesthetic team (anaesthetic consultant or registrar) looking after the patient from the arterial line (if available) or else through standard phlebotomy technique straight from a vein.
Samples 2 and 3 will be taken by the autotransfusionist from the intraoperative cell salvage circuit.
Sample 5 will be taken through standard phlebotomy by an anaesthetist or research nurse in the ward on day 3.

The third part of the study will investigate whether cell salvage can reduce immune modulation associated with transfusion. For this assessment, an in vitro transfusion model previously established at the Blood Service, will be used. Briefly, pre-surgery patient blood (sample 1) will be cultured with cell salvage product (sample 3) or ABO compatible allogenic blood (provided by the Blood Service). In parallel, responses to bacterial infection will be modelled using lipopolysaccharide (LPS). Following six hours of exposure, dendritic cell and monocyte specific immune responses will be assessed.
Intervention code [1] 300798 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305405 0
Capacity to respond to model of bacterial infection.
Monocyte and DC maturation markers and production of cytokines and chemokines will be assed using flow cytometry.
Timepoint [1] 305405 0
Time points 1, 4 and 5.
Primary outcome [2] 305666 0
Quantification of immune cell subsets by flow cytometry.
Timepoint [2] 305666 0
Time points 1, 2, 3, 4 and 5.
Primary outcome [3] 305667 0
Quantification of inflammatory mediators in cell salvage product.
Inflammatory mediators will be quantified using cytometric bead array (flow cytometry)
Timepoint [3] 305667 0
Time points 2 and 3.
Secondary outcome [1] 351055 0
Assess the feasibility of a future RCT.
1. Technical Feasibility – determine whether appropriate technical resources were assigned to the project and confirm laboratory outcomes are reproducible.
2. Economic Feasibility – assess cost/ benefits analysis of the project, and determine what staff, capital and consumable resources would be required for a RCT.
Timepoint [1] 351055 0
Time points 1, 2, 3, 4 and 5

Eligibility
Key inclusion criteria
20 patients undergoing orthopaedic procedures, who are scheduled to receive intraoperative cell salvage as per our standard practise and process, will be included.
Inclusion Criteria (as per our standard operating procedure):
1. Patients aged> 18 years.
2. Scheduled for elective Orthopedic procedures with an expected blood loss of more than 1000ml (as per our standard protocol).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1. Pregnant patients.
2. Patient refusal or inability to provide consent.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Firstly, a feasibility or proof-of-principle study in which we will collect samples from orthopaedic surgery ICS (intraoperative cell salvage) patients prior to surgery and post-surgery.
The second part of the study will involve characterisation of the ICS product at different stages of its production.
The third part of the study will involve an in vitro assessment of the potential for TRIM (Transfusion related immune modulation) to be reduced by ICS product compared to allogeneic red cells.
In view of the fact that the study is novel, there is no published data available where the full panel of assays proposed were used to test and compare ABT and ICS responses. Therefore there is no comparable (published) data to base an accurate power analysis and sample size on.
Standard methods such as Bonferroni or Benjamini-Hochberg procedures will be used to address the risk of cumulative alpha error as large data sets with numerous parameters will be analysed.

Recruitment
Recruitment status
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)
QLD
Recruitment hospital [1] 10599 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 22316 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 299124 0
Other Collaborative groups
Name [1] 299124 0
ANZCA Project Grant
Address [1] 299124 0
The Australian and New Zealand College of Anaesthetists
ANZCA House, 630 St Kilda Road, Melbourne VIC 3004, Australia

Country [1] 299124 0
Australia
Funding source category [2] 299126 0
Government body
Name [2] 299126 0
National Blood Authority
Address [2] 299126 0
NBA (National Blood Authority)
Level 2/243 Northbourne Ave, Lyneham ACT 2602
Country [2] 299126 0
Australia
Funding source category [3] 299127 0
Other Collaborative groups
Name [3] 299127 0
Australian Red Cross Blood Service
Address [3] 299127 0
Australian Red Cross Blood Service
44 Musk Ave, Kelvin Grove QLD 4059
Country [3] 299127 0
Australia
Primary sponsor type
Individual
Name
Michelle Roets
Address
Royal Brisbane and Women's Hospital
Bowen Bridge Rd & Butterfield St, Herston QLD 4029
Country
Australia
Secondary sponsor category [1] 298384 0
Individual
Name [1] 298384 0
A/Prof David Sturgess
Address [1] 298384 0
The Princess Alexandra Hospital
199 Ipswich Rd, Woolloongabba QLD 4102
Country [1] 298384 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300058 0
Royal Brisbane and Women’s Hospital Human Research Ethics Committee (RBWH HREC) (EC00172)
Ethics committee address [1] 300058 0
Royal Brisbane and Women’s Hospital
Level 7, Block 7,
Butterfield Street, Herston, QLD, 4029, Australia
Ethics committee country [1] 300058 0
Australia
Date submitted for ethics approval [1] 300058 0
25/11/2017
Approval date [1] 300058 0
06/02/2018
Ethics approval number [1] 300058 0
HREC/17/QRBW/685

Summary
Brief summary
Blood collected from volunteers, also known as allogeneic blood, is donated, processed and made available for patients requiring transfusion, such as during surgery. This is an expensive process; according to the National Blood Authority, the estimated cost associated with blood transfusion in Australia is over $1 billion per year. While the safety of allogeneic blood transfusions has improved over decades, life-threatening risks remain. For example, 617 transfusion-related adverse events were reported in Australia in 2013-2014. These adverse events include wrong blood to wrong patient, transfusion-related lung injury, allergic reaction, infection, cancer recurrence, organ failure and death. Research has linked some of these outcomes to a post-transfusion impairment of the patient’s immune responses. In order to better understand how this happens, the Australian Red Cross Blood Service has developed a series of tests to characterise how transfusion impairs these immune responses.

Intraoperative cell salvage is a process where blood lost during surgery is collected, processed and given back to the patient. Use of intraoperative cell salvage may provide a cost-effective and safer alternative to allogeneic blood transfusion. In particular, because patients aren’t exposed to blood from another person, it seems likely that the impairment of immune responses that occurs following allogeneic blood transfusion will be prevented. However, whether or not this assumption is true remains to be investigated. Therefore this research project aims to investigate whether the process of intraoperative cell salvage affects the immune responses of patients. To do so, this research project will use the existing series of assays already developed by the Australian Red Cross Blood Service.

This project will be highly significant to the health care system as we anticipate that intraoperative cell salvage, as an alternative to allogeneic blood transfusion, results in better patient care, less harm to patients and a decrease in costs. This important research is led by Dr Michelle Roets, a senior anaesthetist at the Royal Brisbane and Women’s Hospital who has been researching improvements in blood management over the past 10 years. Her work has resulted in authorship of the ‘Guidance for the Provision of Intraoperative Cell Salvage’ National documents with the National Blood Authority in Australia. Dr Roets has teamed up with the Australian Red Cross Service to co-ordinate an expert team and evaluate the association between immune suppression and infection risk after allogeneic blood transfusion compared to intraoperative cell salvage. These results hope to significantly improve current blood administration practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82422 0
Dr Michelle Roets
Address 82422 0
Consultant anaesthetist, Anaesthetic department, Level 4, Ned Hanlon Building,
RBWH, Bowen Bridge Rd & Butterfield St, Herston QLD 4029
Country 82422 0
Australia
Phone 82422 0
+61736367154
Fax 82422 0
Email 82422 0
michelle.roets@health.qld.gov.au
Contact person for public queries
Name 82423 0
Dr Michelle Roets
Address 82423 0
Consultant anaesthetist, Anaesthetic department, Level 4, Ned Hanlon Building,
RBWH, Bowen Bridge Rd & Butterfield St, Herston QLD 4029
Country 82423 0
Australia
Phone 82423 0
+61736367154
Fax 82423 0
Email 82423 0
michelle.roets@health.qld.gov.au
Contact person for scientific queries
Name 82424 0
Dr Michelle Roets
Address 82424 0
Anaesthetic department, Level 4, Ned Hanlon Building,
RBWH, Bowen Bridge Rd & Butterfield St, Herston QLD 4029
Country 82424 0
Australia
Phone 82424 0
+61736367154
Fax 82424 0
Email 82424 0
michelle.roets@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Combined data analysis. No individual patient identifying details will be assessed.
What supporting documents are/will be available?
No other documents available
Summary results
No Results