Trial Review

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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
10/12/2020
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
Sex
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
Completed
Date of first participant enrolment
Anticipated
1/09/2018
Actual
30/10/2018
Date of last participant enrolment
Anticipated
31/12/2019
Actual
29/10/2019
Date of last data collection
Anticipated
31/03/2020
Actual
31/03/2020
Sample size
Target
20
Accrual to date
Final
20
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
Country [1] 299124 0
Australia
Funding source category [2] 299126 0
Government body
Name [2] 299126 0
National Blood Authority
Country [2] 299126 0
Australia
Funding source category [3] 299127 0
Other Collaborative groups
Name [3] 299127 0
Australian Red Cross Blood Service
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
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
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
[email protected]
Contact person for public queries
Name 82423 0
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
[email protected]
Contact person for scientific queries
Name 82424 0
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
[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
Combined data analysis. No individual patient identifying details will be assessed.


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
SourceTitleYear of PublicationDOI
EmbaseIntraoperative Cell Salvage as an Alternative to Allogeneic (Donated) Blood Transfusion: A Prospective Observational Evaluation of the Immune Response Profile.2020https://dx.doi.org/10.1177/0963689720966265
EmbaseIntraoperative cell salvage: The impact on immune cell numbers.2023https://dx.doi.org/10.1371/journal.pone.0289177
N.B. These documents automatically identified may not have been verified by the study sponsor.