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Trial registered on ANZCTR


Registration number
ACTRN12620000595910p
Ethics application status
Submitted, not yet approved
Date submitted
24/04/2020
Date registered
22/05/2020
Date last updated
22/05/2020
Date data sharing statement initially provided
22/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Australian and New Zealand Multicenter trial of Extended (6-8 hours) Non-Ischemic Heart Preservation (NIHP) of Donor Hearts for Transplantation
Scientific title
Australian and New Zealand Multicenter trial of Extended (6-8 hours) Non-Ischemic Heart Preservation (NIHP) using the XVIVO heart preservation system of Donor Hearts for Transplantation
Secondary ID [1] 300930 0
Nil
Universal Trial Number (UTN)
Trial acronym
ANZ-NIHP
Linked study record
n/a

Health condition
Health condition(s) or problem(s) studied:
Heart Transplant 316908 0
Chronic Heart Failure 316909 0
Condition category
Condition code
Surgery 315085 315085 0 0
Other surgery
Cardiovascular 315473 315473 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: XVIVO Heart Box/Preservation System.

The XVIVO Heart Box is a general-purpose donor-organ preservation/transport system. It is a non-dedicated system designed to support and maintain any donated organ (e.g., heart, kidney, liver) during transport from the donor to the receiving hospital where the organ will be transplanted into the recipient.

This system will provide technical support functions to keep the organ in as near-physiologic state as possible.

The XVIVO Heart Box/Preservation System consists of three separate devices:

- XVIVO Heart Box (re-usable)
- XVIVO Heart Disposable (single use)
- Supplemented XVIVO Heart Solution (single use)

The heart box is the device controlling the preservation system. The container, organ transport components include the 1) XVIVO Heart Box and 2) XVIVO Heart Disposable. A sterile disposable kit is placed into the heart box and tubes are fitted to the pump and clamp unit in the box. The connectors for gas, temperature and pressure sensors, integrated in the disposable kit, are connected to the box. The disposable reservoir kit is filled with perfusion solution from bags with the sterile heart solution, washed red blood cells and additives. The donor heart is attached to the heart cannula and submerged in the perfusion solution. The temperature of the perfusion solution, the CO2/O2 gas flow supplied to the perfusion solution and the pressure in the coronary arteries are controlled by the heart box during the transportation.

Donor Organ Preservation Solution consists of 1) XVIVO Heart Solution (XHS) and 2) XVIVO Heart Solution Supplement (XHSS). This is a sterile fluid used for hypothermic flushing, transport, and storage of donor organs (e.g., kidney, liver, heart, and pancreas) for transplant. The solution is intended to maintain organ viability until the organ can be implanted in the recipient. After application, this device cannot be reused.

The XVIVO Heart Box will be primed by the procuring surgeon and perfusionist from the transplant recipient hospital, in a controlled environment such as an operating room, pump room or operative prep room. The procuring surgeon will place the donor heart into the XVIVO Heart Box system. The Perfusionist will then travel with the donor heart inside the XVIVO Heart Box system from the donor hospital to the recipient hospital.

The XVIVO Heart Box will be utilised to preserve 36 donor hearts in total. In the initial phase of the trial, 12 donor hearts will be procured and transported with the NIHP method with less than 6 hours of anticipated ischemic time (standard NIHP). The remaining 24 donor hearts will be a projected ischemic time of 6-8 hours (extended NHIP).
Intervention code [1] 317243 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323376 0
Death as determined by prospective assessment, tests and medical records
Timepoint [1] 323376 0
30 days post transplant
Primary outcome [2] 323717 0
Primary graft dysfunction (moderate or severe) (according to Kobashigawa et al 2014) as determined by prospective assessment, tests and medical records,
Timepoint [2] 323717 0
30 days post transplant
Primary outcome [3] 323718 0
Re-transplantation as determined by prospective assessment, tests and medical records,
Timepoint [3] 323718 0
30 days post transplant
Secondary outcome [1] 381694 0
• ICU length of stay as determined by prospective assessment, tests and medical records
Timepoint [1] 381694 0
12 months post transplant
Secondary outcome [2] 382870 0
• Incidence of acute cellular rejection (ACR) and antibody mediated rejection (AMR) as determined by prospective assessment, tests and medical records
Timepoint [2] 382870 0
12 months post transplant
Secondary outcome [3] 382871 0
• Graft function as determined by prospective assessment, tests and medical records.
Timepoint [3] 382871 0
12 months post transplant
Secondary outcome [4] 382872 0
• Incidence of cardiac allograft vasculopathy (CAV) as determined by prospective assessment, tests and medical records.
Timepoint [4] 382872 0
12 months post transplant
Secondary outcome [5] 382873 0
• Re-transplantation as determined by prospective assessment, tests and medical records.
Timepoint [5] 382873 0
12 months post transplant
Secondary outcome [6] 382874 0
• Arrhythmias as determined by prospective assessment, tests and medical records.
Timepoint [6] 382874 0
12 months post transplant
Secondary outcome [7] 382875 0
• Graft function as determined by prospective assessment, tests and medical records.
Timepoint [7] 382875 0
12 months post transplant
Secondary outcome [8] 382876 0
• Need for permanent pacemaker (PPM) as determined by prospective assessment, tests and medical records.
Timepoint [8] 382876 0
12 months post transplant
Secondary outcome [9] 382877 0
• Incidence of serious adverse events (SAEs; need for post-operative mechanical support, dialysis, ICU length of stay, ventilation) as determined by prospective assessment, tests and medical records.
Timepoint [9] 382877 0
12 months post transplant

Eligibility
Key inclusion criteria
Donor Inclusion criteria:
• Age less than or equal to 60 years
• Accepted as heart donor by the transplant team
• Weight 30kg or greater
• Donor brain death

Recipient Inclusion criteria:
• Patients listed for heart transplantation for any indication including those with mechanical circulatory support and congenital heart disease.
• The anticipated ischemic time of < 6 hours for the first 12 hearts (2 per centre) in the trial followed by 6-8 hours for the remaining 24 hearts.
• Signed informed consent form
Minimum age
13 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Donor Exclusion criteria:
• DCD hearts

Recipient Exclusion criteria:
• Previous solid organ transplantation
• Kidney failure eGFR <40 at listing, calculated by CKD-EPI Creatinine, or ultra ltration or dialysis or rapidly deteriorating kidney function due to a diagnosed renal disease
• Coagulopathy due to known hepatic disease or heparin induced thrombocytopenia
• Sepsis syndrome but positive blood culture and on microorganism speci c antimicrobial included
• Incompatible blood group
• Unable to understand the information provided during the informed consent procedure
• Combined organ transplantation candidates
• Patient already consented for another transplant related intervention study
• Patients under pre-transplant desensitisation protocol

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)
n/a
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
n/a
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data analysis will be performed by a trained statistician. To provide an overall estimate of treatment effect, data will be pooled across study centres. Distributions of continuous variables will be assessed for normality and reported (for each time point) as mean ± standard deviation (SD) for parametric data and median (interquartile range or minimum, maximum) for non-parametric data. Categorical variables will be reported using frequencies and percentages.

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)
NSW,QLD,WA,VIC
Recruitment hospital [1] 16261 0
The Alfred - Melbourne
Recruitment hospital [2] 16262 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 16263 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 16264 0
The Prince Charles Hospital - Chermside
Recruitment hospital [5] 16265 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 29805 0
3004 - Melbourne
Recruitment postcode(s) [2] 29806 0
6150 - Murdoch
Recruitment postcode(s) [3] 29807 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 29808 0
4032 - Chermside
Recruitment postcode(s) [5] 29809 0
3052 - Parkville
Recruitment outside Australia
Country [1] 22463 0
New Zealand
State/province [1] 22463 0
Auckland

Funding & Sponsors
Funding source category [1] 305376 0
Commercial sector/Industry
Name [1] 305376 0
XVIVO Perfusion AB
Address [1] 305376 0
Mässans Gata 10
412 51 Göteborg
Country [1] 305376 0
Sweden
Primary sponsor type
Hospital
Name
Alfred Health
Address
Alfred Health
55 Commercial Road
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 305753 0
None
Name [1] 305753 0
Address [1] 305753 0
Country [1] 305753 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305706 0
The Alfred Ethics Committee
Ethics committee address [1] 305706 0
Alfred Health
55 Commercial Rd
Melbourne VIC 3004
Ethics committee country [1] 305706 0
Australia
Date submitted for ethics approval [1] 305706 0
05/02/2020
Approval date [1] 305706 0
Ethics approval number [1] 305706 0

Summary
Brief summary
The time from when a heart is removed from a brain dead organ donor and transplanted into a recipient is known as the ischemic time. This is a critical period of time since the donor heart is not receiving any blood supply, oxygen or nutrition and if the ischemic time becomes prolonged (beyond approximately 4 to 6 hours), the heart may be damaged to the point that it does not work well in the recipient (known as primary graft dysfunction). For the last 50 years of heart transplantation, transportation of the heart during the ischemic time involves stopping the heart by paralysing it chemically and then putting it in ice slush to cool it down and reduce its energy requirements, a technique known as cold static storage (CSS). Recent advances in donor heart preservation have led to the development of a mechanical perfusion system called non-ischemic heart preservation (NIHP). With this system, during the ischemic time, the heart can be continuously perfused with a solution containing hormones, oxygen and some nutrition. Protecting the donor heart using NIHP substantially increases the ischemic time while minimizing the risk of primary graft dysfunction.

The aim of the current trial is to investigate the effectiveness of NIHP to increase the ischemic time of donor hearts to 6 to 8 hours. Findings from this study may demonstrate that NIHP is beneficial in preventing primary graft failure. Additionally, countries the size of Australia and New Zealand where donor hearts are often declined because the ischemic time is unacceptably long, NIHP of the donor heart may allow longer ischemic times and hence increase donor heart availability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101302 0
Prof David McGiffin
Address 101302 0
Alfred Health
55 Commercial Road
Melbourne VIC 3004
Country 101302 0
Australia
Phone 101302 0
+61390762156
Fax 101302 0
Email 101302 0
d.mcgiffin@alfred.org.au
Contact person for public queries
Name 101303 0
Dr Christina Kure
Address 101303 0
Alfred Health
55 Commercial Road
Melbourne VIC 3004
Country 101303 0
Australia
Phone 101303 0
+61390763621
Fax 101303 0
Email 101303 0
c.kure@alfred.org.au
Contact person for scientific queries
Name 101304 0
Prof David McGiffin
Address 101304 0
Alfred Health
55 Commercial Road
Melbourne VIC 3004
Country 101304 0
Australia
Phone 101304 0
+61390762156
Fax 101304 0
Email 101304 0
d.mcgiffin@alfred.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
What supporting documents are/will be available?
Statistical analysis plan
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7548 0
Statistical analysis plan
Citation [1] 7548 0
Link [1] 7548 0
Email [1] 7548 0
c.kure@alfred.org.au
Other [1] 7548 0
Attachment [1] 7548 0
Type [2] 7549 0
Ethical approval
Citation [2] 7549 0
Link [2] 7549 0
Email [2] 7549 0
c.kure@alfred.org.au
Other [2] 7549 0
Attachment [2] 7549 0
Summary results
No Results