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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05898776




Registration number
NCT05898776
Ethics application status
Date submitted
31/05/2023
Date registered
12/06/2023
Date last updated
20/09/2024

Titles & IDs
Public title
10°C Vs 4°C Lung Preservation RCT
Scientific title
Safety of 10°C Lung Preservation Vs. Standard of Care: a Multi-Centre Prospective Non-Inferiority Trial
Secondary ID [1] 0 0
22-5909
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Transplant 0 0
Organ Preservation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Lung transplantation after 10°C donor lung preservation
Treatment: Devices - Lung transplantation after standard ice cooler donor lung preservation

Experimental: 10°C lung preservation -

Active comparator: Standard lung preservation -


Treatment: Devices: Lung transplantation after 10°C donor lung preservation
When suitable donor lungs become available for a, eligible, consented recipient and meet criteria to go straight to transplantation, the lungs randomized to 10°C preservation will be stored, transported and preserved in the X°Port Lung Transport Device (Traferox Technologies Inc.) until implant with a maximum time of 12 hours between the donor and recipient surgeries.

Treatment: Devices: Lung transplantation after standard ice cooler donor lung preservation
When suitable donor lungs become available for a, eligible, consented recipient and meet criteria to go straight to transplantation, the lungs randomized to standard preservation will be will be stored, transported and preserved in an ice cooler (\~4°C, standard of care) until implant with a maximum time of 6 hours between the donor and recipient surgeries.
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Primary Graft Dysfunction (PGD) Grade 3 as per International Society for Heart and Lung Transplantation (ISHLT)
Timepoint [1] 0 0
72 hours post-transplant
Secondary outcome [1] 0 0
Incidence of Primary Graft Dysfunction Grade 2-3 as per International Society for Heart and Lung Transplantation
Timepoint [1] 0 0
0 (ICU arrival), 24, 48, and 72 hours post-transplant
Secondary outcome [2] 0 0
Time on ventilator
Timepoint [2] 0 0
Index hospitalization (up to 1 year)
Secondary outcome [3] 0 0
Total ICU and hospital length of stay
Timepoint [3] 0 0
Index hospitalization (up to 1 year)
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
30 days, 1 year post-transplant
Secondary outcome [5] 0 0
Occurrence of acute rejection
Timepoint [5] 0 0
1 year post-transplant
Secondary outcome [6] 0 0
Six minute walk test
Timepoint [6] 0 0
1 year post-transplant
Secondary outcome [7] 0 0
Forced expiratory volume - one second (FEV1 in L)
Timepoint [7] 0 0
1 year post-transplant

Eligibility
Key inclusion criteria
Donor Inclusion Criteria

* Donation after brain death (DBD) or donation after cardiac death (DCD)
* Donor lungs are suitable to go straight to LTx (i.e., do not need ex vivo lung perfusion (EVLP) assessment)

Donor
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Concerns with organ preservation technique
* Need for EVLP assessment

Recipient Inclusion Criteria

* 18-80 years old
* Primary lung transplantation
* Bilateral lung transplantation

Recipient Exclusion Criteria

* Re-transplantation
* Multi-organ transplantation
* Single lung transplantation
* Participation in a contraindicating trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney Limited - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
Austria
State/province [4] 0 0
Vienna
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Spain
State/province [6] 0 0
Madrid
Country [7] 0 0
Switzerland
State/province [7] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
University Health Network, Toronto
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Medical University of Vienna
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Vanderbilt University
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Puerta de Hierro University Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of California, San Francisco
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Centre Hospitalier Universitaire Vaudois
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Mayo Clinic
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
St Vincent's Hospital, Sydney
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Despite lung transplantation (LTx) being the most effective treatment for end-stage lung disease, its success rate is lower than that of other solid organ transplantations. Primary graft dysfunction (PGD) is the most common post-operative complication and a major factor in early mortality and morbidity, affecting \~25% of lung transplant patients. Induced by ischemia reperfusion, PGD represents a severe and acute lung injury that occurs within the first 72 hours after transplantation, and has a significant impact on short- and long-term outcomes, and a significant increase in treatment costs. Any intervention that reduces the risk of PGD will lead to major improvements in short- and long-term transplant outcomes and health care systems.

One of the main strategies to reduce the risk and severity of post-transplant PGD is to improve pre-transplant donor lung preservation methods. In current practice, lung preservation is typically performed by cold flushing the organ with a specialized preservation solution, followed by subsequent hypothermic storage on ice (\~4°C). This method continues to be used and applied across different organ systems due to its simplicity and low cost. Using this method for the preservation of donor lungs, the current maximum accepted preservation times have been limited to approximately 6-8h. While the goal of hypothermic storage is to sustain cellular viability during ischemic time through reduced cellular metabolism, lower organ temperature has also been shown to progressively favor mitochondrial dysfunction. Therefore, the ideal temperature for donor organ preservation remains to be defined and should maintain a balance between avoidance of mitochondrial dysfunction and prevention of cellular exhaustion. In addition to that, safe and longer preservation times can lead to multiple advantages such as moving overnight transplants to daytime, more flexibility to transplant logistics, more time for proper donor to recipient matching etc.

Building on pre-clinical research suggesting that 10°C may be the optimal lung storage temperature, a prospective, multi-center, non-randomized clinical trial was conducted at University Health Network, Medical University of Vienna and Puerta de Hierro Majadahonda University Hospital. Donor lungs meeting criteria for direct transplantation and with cross clamp times between 6:00pm - 4:00am were intentionally delayed to an earliest allowed start time of 6:00am and a maximum preservation time from donor cold flush to recipient anesthesia start time of 12 hours. Lungs were retrieved and transported in the usual fashion using a cooler with ice and transferred to a 10°C temperature-controlled cooler upon arrival to transplant hospital until implantation. The primary outcome of this study was incidence of Primary Graft Dysfunction (PGD) Grade 3 at 72h, with secondary endpoints including: recipient time on the ventilator, ICU Length of Stay (LOS), hospital LOS, 30-day survival and lung function at 1-year. Outcomes were compared to a contemporaneous conventionally transplanted recipient cohort using propensity score matching at a 1:2 ratio. 70 patients were included in the study arm. Post-transplant outcomes were comparable between the two groups for up to 1 year. Thus, intentional prolongation of donor lung preservation at 10°C was shown to be clinically safe and feasible.

In the current study design, the investigators will conduct a multi-centre, non-inferiority, randomized, controlled trial of 300 participants to compare donor lung preservation from the time of explant to implant at \~10°C in X°Port Lung Transport Device (Traferox Technologies Inc.) vs a standard ice cooler. When eligible donor lungs become available for a consented recipient, the lungs will be randomized to undergo a preservation protocol using either 10°C (X°Port Lung Transport Device, Traferox Technologies Inc.) or standard of care. The primary outcome of the study is incidence of ISHLT Primary Graft Dysfunction Grade 3 at 72 hours. Post-transplant outcomes will be followed for one year.
Trial website
https://clinicaltrials.gov/study/NCT05898776
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Elliot Wakeam, MD MPH
Address 0 0
University Health Network, Toronto
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sharaniyaa Balachandran
Address 0 0
Country 0 0
Phone 0 0
416-340-4800
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05898776