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Trial registered on ANZCTR


Registration number
ACTRN12619001016123
Ethics application status
Approved
Date submitted
24/06/2019
Date registered
15/07/2019
Date last updated
19/11/2020
Date data sharing statement initially provided
15/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Personalising immunosuppression in liver transplantation
Scientific title
Precision medicine in liver transplantation: accuracy of quantiferon monitor and donor specific cell-free DNA (QFM-dscfDNA) in monitoring and managing immunosuppression post liver transplantation
Secondary ID [1] 298581 0
Nil known
Universal Trial Number (UTN)
U1111-1235-8959
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver transplantation 313421 0
Solid organ rejection 313422 0
Infection 313423 0
Condition category
Condition code
Oral and Gastrointestinal 311856 311856 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 311857 311857 0 0
Other inflammatory or immune system disorders
Infection 311858 311858 0 0
Other infectious diseases
Surgery 311925 311925 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This prospective observational cohort study aims to determine the utility of combining two novel blood tests - quantiferon monitor and donor specific cell-free DNA (QFM-dscfDNA) - in monitoring and managing immunosuppression post liver transplantation (LT).

Liver function tests (LFTs) are extremely sensitive tests for organ injury but have poor specificity for LT complications. As a screening tool, they can lead to a series of radiological and endoscopic investigations that often culminate in an invasive liver biopsy to confirm the clinical event. Researchers at Austin Health have therefore pioneered the study of two rapid and low-cost blood tests in LT: QFM which measures the immune function of the recipient, and dscfDNA which quantifies injury to the donor organ.

For this study, adults (aged 18 years and older) undergoing LT at a tertiary hospital will be invited to participate in this study in the inpatient and outpatient setting. Study co-ordinators (clinicians who are not members of the treating team) will meet with potential participants face-to-face and provide them with written information about the study. Participants who provide written informed consent will be followed up for 12 months and will be required to have serial additional blood sampling. This will be performed by experienced phlebotimists when blood tests for the standard of care for LT occur wherever possible, to reduce the need for additional venesection. 15-30ml of blood will be collected to perform QFM-dscfDNA testing and be stored for future research purposes. Blood sampling will occur pre-transplantation and post-transplant on day 1, 3 and 5; week 1 and 2; month 1, 2, 4, 6 and 12. If an episode of treatment responsive biopsy proven acute rejection (tBPAR) or infection occurs, blood sampling will occur and at three timepoints 1-3 days apart to capture QFM-dscfDNA dynamics. All samples will be batched for analysis at the end of the 12-month follow-up, so results will not influence the decision-making of the treating clinicians.

In the event that a patient is unwell and unable to consent (which may happen for example in fulminant hepatic failure), consent for initial enrolment will be obtained from the next of kin/medical treatment decision maker. Following recovery from the LT, patient consent for ongoing follow up and for use of data collected at enrolment will be obtained. If the patient wishes to withdraw the consent obtained from their next of kin/medical treatment decision maker, all of the data collected for research purposes will be destroyed.
Intervention code [1] 314845 0
Diagnosis / Prognosis
Comparator / control treatment
LFTs
Control group
Active

Outcomes
Primary outcome [1] 320528 0
The accuracy of QFM and dscfDNA, alone and in combination, compared to LFTs to diagnose: the first episode of tBPAR, as measured by the area under the receiver operator
curve (AUC) established according to liver biopsy and medical records.
Timepoint [1] 320528 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).

No timepoint is considered to be primary.
Primary outcome [2] 320657 0
The accuracy of QFM and dscfDNA, alone and in combination, compared to LFTs to diagnose the first episode of infective complication, as measured by the AUC established according to medical records.
Timepoint [2] 320657 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).

No timepoint is considered to be primary.
Secondary outcome [1] 371928 0
The accuracy of QFM and dscfDNA, alone and in combination, in predicting the
occurrence of imminent tBPAR before clinical manifestation of the event, compared to LFTs established according to liver biopsy and medical records.
Timepoint [1] 371928 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).
Secondary outcome [2] 372137 0
The accuracy of QFM and dscfDNA, alone and in combination, in predicting the
occurrence of infective complications before clinical manifestation of the event, compared to LFTs established according to medical records.
Timepoint [2] 372137 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).
Secondary outcome [3] 372138 0
The performance of QFM and dscfDNA, alone and in combination, in monitoring treatment responses of tBPAR, compared to LFTs, established according to liver biopsy and medical records.
Timepoint [3] 372138 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).
Secondary outcome [4] 372357 0
The performance of QFM and dscfDNA, alone and in combination, in monitoring
treatment responses of infective complications, compared to LFTs, established according to medical records.
Timepoint [4] 372357 0
Pre-transplantation, post-transplant (day 1, 3 and 5; week 1 and 2; month 1, 2 4, 6 and 12) and at if an episode of tBPAR or infection occurs (3 timepoints, 1-3 days apart).
Secondary outcome [5] 372358 0
Healthcare expenditures of QFM-dscfDNA measured using hospital, PBS and MBS data, as compared to routine medical care (including LFTs, medical imaging, liver biopsies).
Timepoint [5] 372358 0
12 months post-transplant

Eligibility
Key inclusion criteria
• Age 18 years and above.
• Undergoing LT at Austin Health.
• Can provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Aged under 18 years.
• Undergoing multi-organ transplantation.
• Unable to provide written informed consent at any stage.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We propose enrolling a total of 210 LT recipients during a three-year recruitment period.

This timeframe is anticipated to be easily feasible as the LTU performs an average of 75 adult LTs each year. Most recipients will fulfil the trial’s inclusion and exclusion criteria; hence noneligibility (including refusal of informed consent) is anticipated to be low (about 5%). In addition, lost-to-follow-up (including death) is anticipated to be very low (about 1-2%) during the 12-month follow-up.

In preliminary research from Austin Health, 31% of the recipients experienced tBPAR as
the first event after LT while 41% experienced a ‘probable’/’definite’ infective complication as the first event after LT, both within a 12-month follow-up period. To be conservative, we
assume 30% of our recruited recipients will experience at least one tBPAR and 40% at least
one infective complication. The sample size of 210 LT recipients will allow us to estimate a
fair AUC of 0.7 using a two-sided 95% confidence interval with precision ± 0.081 for tBPAR
and ± 0.075 for infection and a good AUC of 0.8 with a precision of ± 0.075 for tBPAR and ±
0.069 for infection.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/07/2019
Actual
24/07/2019
Date of last participant enrolment
Anticipated
1/08/2021
Actual
Date of last data collection
Anticipated
1/09/2022
Actual
Sample size
Target
210
Accrual to date
22
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14083 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 26874 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 303122 0
Self funded/Unfunded
Name [1] 303122 0
Country [1] 303122 0
Primary sponsor type
Individual
Name
A/Prof Vijayaragavan Muralidharan
Address
Level 8 Lance Townsend Building, Austin Health
145 Studley Rd, Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 303175 0
Individual
Name [1] 303175 0
Dr Tess McClure
Address [1] 303175 0
Level 8 Harold Stokes Building, Austin Health
145 Studley Rd, Heidelberg VIC 3084
Country [1] 303175 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303673 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 303673 0
145 Studley Rd, Heidelberg VIC 3084
Ethics committee country [1] 303673 0
Australia
Date submitted for ethics approval [1] 303673 0
29/01/2019
Approval date [1] 303673 0
14/06/2019
Ethics approval number [1] 303673 0
HREC/50856/Austin-2019
Ethics committee name [2] 303675 0
Australian Red Cross Blood Service Ethics Committee
Ethics committee address [2] 303675 0
17 O'Riordan Street Alexandria NSW 2015
Ethics committee country [2] 303675 0
Australia
Date submitted for ethics approval [2] 303675 0
Approval date [2] 303675 0
11/07/2019
Ethics approval number [2] 303675 0
McClure 11072019

Summary
Brief summary
We propose a prospective cohort study of 210 adult liver transplant recipients followed up for 12-months, to determine the utility of combining two novel blood tests - quantiferon monitor and donor-specific cell free DNA (QFMdscfDNA) - in monitoring and managing immunosuppression post liver transplantation.

Our primary hypothesis is that the QFM-dscfDNA tests can be used to accurately diagnose the occurrence of rejection or infective complications after liver transplantation. The secondary hypotheses are that the QFM-dscfDNA tests can be used to predict acute rejection or infective complications, monitor treatment responses and improve healthcare resource utilisation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94450 0
A/Prof Vijayaragavan Muralidharan
Address 94450 0
Level 8 Lance Townsend Building, Austin Health
145 Studley Rd, Heidelberg VIC 3084
Country 94450 0
Australia
Phone 94450 0
+61394965000
Fax 94450 0
Email 94450 0
v.muralidharan@unimelb.edu.au
Contact person for public queries
Name 94451 0
Dr Tess McClure
Address 94451 0
Level 8 Harold Stokes Building, Austin Health
145 Studley Rd, Heidelberg VIC 3084
Country 94451 0
Australia
Phone 94451 0
+61394965353
Fax 94451 0
Email 94451 0
tess.mcclure@austin.org.au
Contact person for scientific queries
Name 94452 0
Dr Tess McClure
Address 94452 0
Level 8 Harold Stokes Building, Austin Health
145 Studley Rd, Heidelberg VIC 3084
Country 94452 0
Australia
Phone 94452 0
+61394965353
Fax 94452 0
Email 94452 0
tess.mcclure@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No identifiable individual information will be presented in any publication. Any papers arising
from this project will provide de-identified or cohort information only.


What supporting documents are/will be available?




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.