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Trial registered on ANZCTR


Registration number
ACTRN12623000301662p
Ethics application status
Not yet submitted
Date submitted
8/03/2023
Date registered
17/03/2023
Date last updated
17/03/2023
Date data sharing statement initially provided
17/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Marine oxygen carrier (M101) for organ preservation in liver transplantation; a randomised exploratory study.
Scientific title
The effect of marine oxygen carrier (M101) during cold static storage on the incidence of ischaemia reperfusion injury in liver transplantation; a randomised exploratory study.
Secondary ID [1] 309062 0
Nil known
Universal Trial Number (UTN)
U1111-1288-7725
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Transplantation 329122 0
Condition category
Condition code
Surgery 326094 326094 0 0
Other surgery
Oral and Gastrointestinal 326095 326095 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We will assess outcome after liver transplantation using grafts from deceased donors after brain death that have been perfused with University of Wisconsin solution (UWS) plus the oxygen carrier molecule M101 (HemO2life, Morlaix, France). M101 will be added to UWS that is flushed through the graft on a side table prior to cold static storage. All other donor and transplant procedures and post-transplant care will be standard in accordance with New Zealand Liver Transplant Unit protocol.
Intervention code [1] 325504 0
Treatment: Devices
Comparator / control treatment
The control patients will receive a deceased donor liver graft from a brain dead donor that has been flushed on the side table with UWS, without the addition of M101.
Control group
Active

Outcomes
Primary outcome [1] 333975 0
Assessment of early allograft function according to the L-GrAFT7 score (derived from day 1-7 AST, INR, bilirubin and platelet count blood tests).
Timepoint [1] 333975 0
Day 7 post-transplant
Secondary outcome [1] 418900 0
Reperfusion syndrome, assessed according to Aggarwal criteria, from the anaesthesia record.
Timepoint [1] 418900 0
Intra-operative, at time of graft reperfusion.
Secondary outcome [2] 418901 0
Histological assessment of ischaemia reperfusion injury on post-reperfusion liver biopsy.
Timepoint [2] 418901 0
Graft biopsy prior to abdominal closure
Secondary outcome [3] 418902 0
Acute kidney injury according to Kidney Disease Improving Global Outcomes definition, assessed by serum creatinine levels.
Timepoint [3] 418902 0
Daily blood tests post-operative day 1-7.
Secondary outcome [4] 418903 0
Biliary complications (leak, anastomotic or non-anastomic stricture) defined by cholangiography (MRC, ERCP or PTC) in combination with clinical symptoms and/or elevation of cholestatic liver tests.
Timepoint [4] 418903 0
Post-operative, within 1 year of transplant.
Secondary outcome [5] 418904 0
Vascular complications; stenosis or thrombosis diagnosed on Doppler ultrasound, CT or MRI or at re-exploration.
Timepoint [5] 418904 0
Post-operative, within 1 year of post transplant.
Secondary outcome [6] 418905 0
Complications according to Dindo-Clavien Classification, plus Comprehensive Complication Index (for example, post-operative pneumonia Grade II, re-operation for bleeding is Grade IIIb).
Timepoint [6] 418905 0
Post-operative, within 30 days.
Secondary outcome [7] 418906 0
Acute cellular rejection, proven on liver graft biopsy.
Timepoint [7] 418906 0
Post-operative, within 1 year of transplant.
Secondary outcome [8] 418907 0
Graft survival, assessed by data-linkage to medical records.
Timepoint [8] 418907 0
1 year after transplant
Secondary outcome [9] 418908 0
Patient survival, assessed by data-linkage to medical records.
Timepoint [9] 418908 0
1 year after transplant
Secondary outcome [10] 419526 0
Assays of mitochondrial function and oxidate stress on graft biopsies.
Timepoint [10] 419526 0
End-ischaemic graft biopsy, and post-reperfusion graft biopsy.
Secondary outcome [11] 419528 0
Cellular immunity assay (iNKT cells, NK cells, myeloid cells, conventional T cells, TReg cells) by flow cytometry of blood samples.
Timepoint [11] 419528 0
During transplant surgery (pre and post implantation), day 3 and day 7 post-operative.
Secondary outcome [12] 419531 0
Cytokine assays on blood samples (IL-33, HMGB-1, IL-6, IL-2, IL-18, sST2, amphiregulin, meteorin).
Timepoint [12] 419531 0
During transplant surgery (pre and post implantation), day 3 and day 7 post-operative.

Eligibility
Key inclusion criteria
Standard criteria graft from brain death deceased donor
Adult recipient of first liver transplant
Able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Donation after circulatory death or extended criteria graft
Re-transplantation
Acute liver failure
Split liver transplant

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is an exploratory or pilot study in liver transplantation, hence there is no sample size calculation. The primary outcome is a continuous variable and will be compared between intervention and control groups using unpaired Student t-test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2023
Actual
Date of last participant enrolment
Anticipated
1/08/2024
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 25287 0
New Zealand
State/province [1] 25287 0

Funding & Sponsors
Funding source category [1] 313267 0
Self funded/Unfunded
Name [1] 313267 0
Country [1] 313267 0
Primary sponsor type
Individual
Name
A/Prof Louise Barbier
Address
New Zealand Liver Transplant Unit
Te Toka Tumai - Auckland
2 Park Avenue
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 315002 0
Individual
Name [1] 315002 0
Prof John McCall
Address [1] 315002 0
New Zealand Liver Transplant Unit
Te Toka Tumai - Auckland
2 Park Avenue
Grafton
Auckland 1023
Country [1] 315002 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 312497 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 312497 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 312497 0
New Zealand
Date submitted for ethics approval [1] 312497 0
31/03/2023
Approval date [1] 312497 0
Ethics approval number [1] 312497 0

Summary
Brief summary
Liver transplantation requires the donor liver to be stored for the period of time between being removed from the donor and transplanted into a recipient. This storage period can be up to 12 hours and during this time the liver does not receive any oxygen. Even though the liver is stored on ice, the lack of oxygen can result in injury to the liver cells and impair recovery after the transplant. M101 is a recently discovered oxygen carrying molecule with properties that make it very well suited for organ preservation. M101 will be added to the preservation fluid to provide oxygen during the period of storage, in order to prevent injury to liver cells from lack of oxygen. Studies in kidney transplantation found M101 to be safe and have a beneficial effect on kidney recovery after transplantation. M101 has also shown promising results in animal models of liver transplantation. However, it has not yet been tested in human liver transplantation.
We would like to test whether adding M101 to the preservation fluid during storage of the donor liver improves liver function and patient recovery after the transplant. We will also assess whether M101 improves mitochondrial function (mitochondria are inside the liver cells and convert oxygen into the energy that the cells need to function) and modifies the immune response (which is activated by cell damage due to lack of oxygen).
We hope that this research will lead to ways to improve the preservation of liver grafts used for transplantation, and that this will lead to better outcomes for patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124874 0
A/Prof Louise Barbier
Address 124874 0
New Zealand Liver Transplant Unit
Te Toka Tumai - Auckland
2 Park Avenue
Grafton
Auckland 1023
Country 124874 0
New Zealand
Phone 124874 0
+64 21395937
Fax 124874 0
Email 124874 0
[email protected]
Contact person for public queries
Name 124875 0
Louise Barbier
Address 124875 0
New Zealand Liver Transplant Unit
Te Toka Tumai - Auckland
2 Park Avenue
Grafton
Auckland 1023
Country 124875 0
New Zealand
Phone 124875 0
+64 21395937
Fax 124875 0
Email 124875 0
[email protected]
Contact person for scientific queries
Name 124876 0
Louise Barbier
Address 124876 0
New Zealand Liver Transplant Unit
Te Toka Tumai - Auckland
2 Park Avenue
Grafton
Auckland 1023
Country 124876 0
New Zealand
Phone 124876 0
+64 21395937
Fax 124876 0
Email 124876 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
This is a small trial in a distinct patient population and despite de-identification there is a risk that IPD could lead to inadvertent identification of individual participants.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18427Study protocol  [email protected]
18428Informed consent form  [email protected]
18429Statistical analysis plan  [email protected]
18430Clinical study report  [email protected]
18431Ethical approval  [email protected]



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.