10°C vs 4°C Lung Preservation RCT

NCT05898776 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 22-5909
• Study Type: interventional
• Target: 317
• Locations: 7 countries
• Sites: 16

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.

Conditions

Lung Transplant; Organ Preservation

Outcome Measures

Primary Outcomes (1)

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

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

  72 hours post-transplant

Secondary Outcomes (7)

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

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

• Time on ventilator

  Index hospitalization (up to 1 year)

• Total ICU and hospital length of stay

  Index hospitalization (up to 1 year)

• Overall survival

  30 days, 1 year post-transplant

• Occurrence of acute rejection

  1 year post-transplant

Study Arms (2)

10°C lung preservation

EXPERIMENTAL

Device: Lung transplantation after 10°C donor lung preservation

Standard lung preservation

ACTIVE COMPARATOR

Device: Lung transplantation after standard ice cooler donor lung preservation

Interventions

Lung transplantation after 10°C donor lung preservation DEVICE

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.

10°C lung preservation

Lung transplantation after standard ice cooler donor lung preservation DEVICE

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.

Standard lung preservation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Concerns with organ preservation technique
• Need for EVLP assessment
• years old
• Primary lung transplantation
• Bilateral lung transplantation
• Re-transplantation
• Multi-organ transplantation
• Single lung transplantation
• Participation in a contraindicating trial

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Medical University of Vienna: collaborator
• Vanderbilt University: collaborator
• Puerta de Hierro University Hospital: collaborator
• University of California, San Francisco: collaborator
• Dignity Health: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• Mayo Clinic: collaborator
• St Vincent's Hospital, Sydney: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Corewell Health West: collaborator
• University of Miami: collaborator
• University Hospital of Leuven Leuven: collaborator
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• University Hospital, Zürich: collaborator
• Hospital Universitario 12 de Octubre: collaborator
• Marie Lannelongue Hospital, Le Plessis Robinson, France: collaborator

Study Sites (17)

Dignity Health (St. Joseph's Hospital and Medical Center)

Phoenix, Arizona, 85050, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

Corewell Health Research Institute

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

St Vincent's Hospital Sydney Limited

Sydney, New South Wales, 2010, Australia

Location

Medical University of Vienna

Vienna, Austria

Location

University Hospitals Leuven

Leuven, Belgium

Location

University Health Network (Toronto General Hospital)

Toronto, Ontario, M5G 2C4, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X0A9, Canada

Location

The Saint Joseph Hospital Foundation (Hôpital Marie Lannelongue)

Paris, 75014, France

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro-Majadahonda

Madrid, Spain

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

Location

University Hospital Zurich

Zurich, Switzerland

Location

Study Officials

• Elliot Wakeam, MD MPH

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 12, 2023
• Study Start: June 9, 2023
• Primary Completion: November 24, 2025
• Study Completion (Estimated): November 22, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

FR (1); BE (1); AU (1); CA (2); CH (2); ES (2); US (7)