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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]

22-5909

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Lung Transplant

Organ Preservation

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]

Treatment: Devices

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Incidence of Primary Graft Dysfunction (PGD) Grade 3 as per International Society for Heart and Lung Transplantation (ISHLT)

Assessment method [1]

PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.

Timepoint [1]

72 hours post-transplant

Secondary outcome [1]

Incidence of Primary Graft Dysfunction Grade 2-3 as per International Society for Heart and Lung Transplantation

Assessment method [1]

PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.

Timepoint [1]

0 (ICU arrival), 24, 48, and 72 hours post-transplant

Secondary outcome [2]

Time on ventilator

Assessment method [2]

Timepoint [2]

Index hospitalization (up to 1 year)

Secondary outcome [3]

Total ICU and hospital length of stay

Assessment method [3]

Timepoint [3]

Index hospitalization (up to 1 year)

Secondary outcome [4]

Overall survival

Assessment method [4]

Timepoint [4]

30 days, 1 year post-transplant

Secondary outcome [5]

Occurrence of acute rejection

Assessment method [5]

Timepoint [5]

1 year post-transplant

Secondary outcome [6]

Six minute walk test

Assessment method [6]

Timepoint [6]

1 year post-transplant

Secondary outcome [7]

Forced expiratory volume - one second (FEV1 in L)

Assessment method [7]

Timepoint [7]

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?

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]

St Vincent's Hospital Sydney Limited - Sydney

Recruitment postcode(s) [1]

2010 - Sydney

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Minnesota

Country [3]

United States of America

State/province [3]

Tennessee

Country [4]

Austria

State/province [4]

Vienna

Country [5]

Canada

State/province [5]

Ontario

Country [6]

Spain

State/province [6]

Madrid

Country [7]

Switzerland

State/province [7]

Lausanne

Funding & Sponsors

Primary sponsor type

Other

Name

University Health Network, Toronto

Country

Other collaborator category [1]

Other

Name [1]

Medical University of Vienna

Country [1]

Other collaborator category [2]

Other

Name [2]

Vanderbilt University

Country [2]

Other collaborator category [3]

Other

Name [3]

Puerta de Hierro University Hospital

Country [3]

Other collaborator category [4]

Other

Name [4]

University of California, San Francisco

Country [4]

Other collaborator category [5]

Other

Name [5]

Centre Hospitalier Universitaire Vaudois

Country [5]

Other collaborator category [6]

Other

Name [6]

Mayo Clinic

Country [6]

Other collaborator category [7]

Other

Name [7]

St Vincent's Hospital, Sydney

Country [7]

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

Public notes

Contacts

Principal investigator

Name

Elliot Wakeam, MD MPH

Address

University Health Network, Toronto

Country

Phone

Contact person for public queries

Name

Sharaniyaa Balachandran

Address

Country

Phone

416-340-4800

sharaniyaa.balachandran@uhn.ca

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05898776

Trial Review

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