Clinical trial NCT05898776: 10°C vs 4°C Lung Preservation RCT
Official title: Safety of 10°C Lung Preservation vs. Standard of Care: A Multi-Centre Prospective Non-Inferiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Transplant
Organ Preservation
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
name: Vanderbilt University
name: Puerta de Hierro University Hospital
name: University of California, San Francisco
name: Centre Hospitalier Universitaire Vaudois
name: Mayo Clinic
name: St Vincent's Hospital, Sydney
name: University of Texas Southwestern Medical Center
name: Spectrum Health Hospitals
name: University of Miami
name: University Hospital of Leuven Leuven
name: Centre hospitalier de l'Université de Montréal (CHUM)
name: University Hospital, Zürich
First posted: 2023-06-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Incidence of Primary Graft Dysfunction (PGD) Grade 3 as per International Society for Heart and Lung Transplantation (ISHLT)
timeFrame: 72 hours post-transplant
Secondary outcomes:
measure: Incidence of Primary Graft Dysfunction Grade 2-3 as per International Society for Heart and Lung Transplantation
timeFrame: 0 (ICU arrival), 24, 48, and 72 hours post-transplant
measure: Time on ventilator
timeFrame: Index hospitalization (up to 1 year)
measure: Total ICU and hospital length of stay
timeFrame: Index hospitalization (up to 1 year)
measure: Overall survival
timeFrame: 30 days, 1 year post-transplant
measure: Occurrence of acute rejection
timeFrame: 1 year post-transplant
measure: Six minute walk test
timeFrame: 1 year post-transplant
measure: Forced expiratory volume - one second (FEV1 in L)
timeFrame: 1 year post-transplant
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Grand Rapids
country: United States
facility: Corewell Health Research Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Sydney
country: Australia
facility: St Vincent's Hospital Sydney Limited
state: New South Wales
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Toronto
country: Canada
facility: University Health Network (Toronto General Hospital)
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Health Network, Toronto
name: Elliot Wakeam, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: