10°C vs 4°C Lung Preservation RCT

Not Applicable

Recruiting

• Conditions: Lung Transplant; Organ Preservation
• Interventions: Device: Lung transplantation after standard ice cooler donor lung preservation; Device: Lung transplantation after 10°C donor lung preservation

• Registration Number: NCT05898776
• Lead Sponsor: University Health Network, Toronto

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-31
• Study Start: 2023-06-09
• Study First Submitted QC: 2023-06-09
• Study First Posted: 2023-06-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-06
• Primary Completion: 2025-07-31
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard lung preservation	Lung transplantation after standard ice cooler donor lung preservation	-
10°C lung preservation	Lung transplantation after 10°C donor lung preservation	-

Primary Outcome Measures

Name	Time	Method
Incidence of Primary Graft Dysfunction (PGD) Grade 3 as per International Society for Heart and Lung Transplantation (ISHLT)	72 hours post-transplant	PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.

Secondary Outcome Measures

Name	Time	Method
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	PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.
Occurrence of acute rejection	1 year post-transplant
Six minute walk test	1 year post-transplant
Forced expiratory volume - one second (FEV1 in L)	1 year 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

Trial Locations

Locations (8)

St Vincent's Hospital Sydney Limited; 🇦🇺 Sydney, New South Wales, Australia

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Medical University of Vienna; 🇦🇹 Vienna, Austria

University Health Network (Toronto General Hospital); 🇨🇦 Toronto, Ontario, Canada

Hospital Universitario Puerta de Hierro-Majadahonda; 🇪🇸 Madrid, Spain

Centre Hospitalier Universitaire Vaudois (CHUV); 🇨🇭 Lausanne, Switzerland