Cold Lung Preservation for Lung Transplant

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Elliot Wakeam, MD MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University Health Network, Toronto

Disqualifiers: Re-transplantation, Multi-organ, Single lung, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Lung transplantation after 10°C donor lung preservation?

Research suggests that storing donor lungs at 10°C may improve lung transplant outcomes by extending the time lungs can be preserved before transplantation, potentially leading to better survival rates and lung function compared to traditional ice storage methods. ^{1 2 3 4 5}

Is cold lung preservation at 10°C safe for lung transplants?

Research suggests that preserving donor lungs at 10°C may be a promising method for lung transplants, potentially offering better outcomes compared to traditional ice storage. However, specific safety data for humans is not detailed in the available studies, and most research has been conducted on animal models. ^{1 2 3 4 6}

What makes the 10°C lung preservation treatment unique for lung transplantation?

The 10°C lung preservation treatment is unique because it allows donor lungs to be stored at a slightly higher temperature than the traditional ice-cold method, potentially extending the time the lungs can be preserved before transplantation, which can improve logistics and outcomes. ^{1 3 5 7 8}

Eligibility Criteria

This trial is for lung transplant recipients whose donor lungs are suitable for immediate transplantation without needing extra assessment. Donors can be after brain or cardiac death, but the lungs must not require ex vivo lung perfusion evaluation.

Inclusion Criteria

I have had a double lung transplant.

My organ donation will be after brain or heart stops.

I am between 18 and 80 years old.

Exclusion Criteria

I am interested in treatments that save my organs.

Re-transplantation

Participation in a contraindicating trial

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Donor lungs are preserved at either 10°C using the X°Port Lung Transport Device or at standard ice cooler temperatures, followed by transplantation.

12 hours

1 visit (in-person)

Post-transplant Monitoring

Participants are monitored for incidence of Primary Graft Dysfunction (PGD) Grade 3 at 72 hours post-transplant.

72 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recipient time on the ventilator, ICU Length of Stay, hospital Length of Stay, 30-day survival, and lung function at 1-year.

1 year

Treatment Details

Interventions

• Lung transplantation after 10°C donor lung preservation (Other)
• Lung transplantation after standard ice cooler donor lung preservation (Other)

Trial Overview The study compares two methods of preserving donor lungs before a transplant: one uses a new device to keep the lungs at about 10°C, and the other uses standard ice cooler preservation at approximately 4°C. The goal is to see if the new method reduces severe lung injury post-transplant.

Participant Groups

Group I: 10°C lung preservation Experimental Treatment 1 Intervention

Group II: Standard lung preservation Active Control 1 Intervention

Lung transplantation after 10°C donor lung preservation is already approved in Canada, European Union, United States for the following indications:

🇨🇦 Approved in Canada as Lung transplantation after 10°C donor lung preservation for:

• End-stage lung disease

🇪🇺 Approved in European Union as Lung transplantation after 10°C donor lung preservation for:

• End-stage lung disease

🇺🇸 Approved in United States as Lung transplantation after 10°C donor lung preservation for:

• End-stage lung disease

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Rochester, MN

University of California San Francisco San Francisco, CA

Vanderbilt University Medical Center Nashville, TN

University Health Network (Toronto General Hospital) Toronto, Canada

Who Is Running the Clinical Trial?

University Health Network, Toronto Lead Sponsor

Puerta de Hierro University Hospital Collaborator

Centre Hospitalier Universitaire Vaudois Collaborator

St Vincent's Hospital, Sydney Collaborator

Vanderbilt University Collaborator

University of California, San Francisco Collaborator

Mayo Clinic Collaborator

Northwestern University Collaborator

Geneve University Collaborator

Hôpital Marie Lannelongue Collaborator

References

1. Spain pubmed.ncbi.nlm.nih.gov

Donor lungs cold preservation at 10 °C offers a potential logistic advantage in lung transplantation. [2023] Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Lung preservation: a review of current practice and future directions. [2019] During the past 10 years, pulmonary transplantation has emerged as a successful mode of surgical therapy for suitable patients with end-stage lung disease. Current preservation techniques of donor lungs for subsequent transplantation include core-cooling and single flush perfusion. The relative merits of these are described. These methods are essentially restricted to 6 hours of ischemia. Research in lung preservation is aimed not only at extending the safe period of ischemia but also at improving the quality of preservation. Areas of interest include the ideal composition of the perfusate, relevant pharmacologic additives, and the best conditions for preservation and harvesting. Advantages and disadvantages of the various animal models are listed in addition to the methods used in assessing the quality of preservation. There have been major advances in experimental lung preservation during the past 10 years, and we are possibly on the threshold of incorporating some of these into clinical practice. Among the most important are the adoption of colloid-based perfusates, the more widespread use of free radical scavengers, and the use of leukocyte depletion.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Improved lung preservation with cold air storage. [2019] Conventional topical slush cooling limits lung transport to 4 to 6 hours. For this canine study of an alternate air cooling system, 37 canine lungs were removed: 24 were placed in plastic bags, and inserted in a Transplanthermm container at core air temperatures (n = 6 lungs each) of (A) 4 degrees C, (B) 8 degrees C, (C) 12 degrees C, and (D) 20 degrees C; 6 were stored conventionally in ice slush (E); and 7 were transplanted immediately (F). After 8 hours, the stored lungs were transplanted and the contralateral pulmonary artery was ligated. Survival, arterial oxygen tension, and extravascular lung water were monitored at 15 minutes and every hour for 4 hours. Four-hour survival was 100% in groups A, B, and F; 83% in group C, 50% in group D, and 17% in group E. The mean arterial oxygen tension at 1 hour was lower in group E (6.4 +/- 2.4 kPa) than in group A (39.8 +/- 13.2 kPa) (p = 0.0002) or in group F (42.0 +/- 16.2 kPa) (p = 0.0035). Extravascular lung water in group E was higher at 15 minutes (15.44 +/- 5.63 mL/kg) than in group A (3.76 +/- 0.63 mL/kg) (p = 0.0001) and group F (4.69 +/- 1.65 mL/kg) (p = 0.003). Cold air storage appears to provide better lung preservation than hypothermic immersion in ice slush.

4. United States pubmed.ncbi.nlm.nih.gov

Assessment of injury in transplanted and nontransplanted lungs after 6 h of cold storage with glutathione. [2017] Single-lung transplantation after 3 h of hypothermic storage produces bilateral lung injury [pulmonary reimplantation response (PRR)]. We hypothesized that glutathione (GSH) hypothermic storage would protect both lungs from PRR for extended preservation times and that differences in injury and protection would be realized between the graft and the nontransplanted lung. Mongrel dogs underwent left single-lung autotransplantation after preservation for 5-6 h in Euro-Collins (EC) solution, EC plus exogenous GSH (EC+GSH), or Viaspan (VIA) at 4 degrees C. Lung injury was measured in both lungs after 1 h of reperfusion. EC dogs demonstrated significant increases in lung edema, lipid peroxidation, and alveolar neutrophil recruitment in the lung graft and to a less extent in the nontransplanted right lung compared with control dogs (P

5. Switzerland pubmed.ncbi.nlm.nih.gov

Flush at room temperature followed by storage on ice creates the best lung graft preservation in rats. [2013] Current clinical lung preservation techniques have not eliminated ischaemia-reperfusion (I/R) injury, despite many improvements. The optimal combination of flush and storage temperatures remain unclear in lung preservation. This is the first study to investigate a range of temperatures with 24-h inflated storage using consistent state-of-the-art preservation techniques. A rat lung transplant model was used to investigate the optimal combination of flush and storage temperatures. In six groups, rat lungs were flushed at 4 °C, 10 °C or room temperature (F(4) /F(10) /F(Rt)) with Perfadex and stored inflated for 24 h in Perfadex on melting ice or at 10 °C (S(ice) /S(10)). Left donor lungs were transplanted for analysis. During 2-h reperfusion, the lung graft function was measured (blood gases, maximum ventilation pressure and static compliance) and lung graft injury was also assessed (W/D ratio, total lung protein, Tryptase, Myeloperoxidase). Right donor lungs were assessed for W/D ratio only after flush and storage. For baseline measurements, left lungs without intervention were used. The combination of F(Rt) -S(ice) showed a significantly higher pO(2), lower P(max), low W/D ratios and total protein levels of left lungs after reperfusion when compared with F(4) -S(ice) and baseline. Storage at 10 °C did not improve preservation. We conclude that F(Rt) -S(ice) creates the best lung graft preservation.

6. United States pubmed.ncbi.nlm.nih.gov

Lung preservation: from perfusion to temperature. [2023] This article will review the evidence behind elements of the lung preservation process that have remained relatively stable over the past decade as well as summarize recent developments in ex-vivo lung perfusion and new research challenging the standard temperature for static cold storage.

7. England pubmed.ncbi.nlm.nih.gov

Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients. [2022] Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs.

8. United States pubmed.ncbi.nlm.nih.gov

Hypothermic storage alone in lung preservation for transplantation: a metabolic, light microscopic, and functional analysis after 18 hours of preservation. [2019] Current lung preservation consists of flushing of the donor organs, with successive hypothermic storage in an inflated state. Recently, hypothermic storage alone was reported to be superior in terms of functional recovery. This study was designed to investigate the metabolic, morphologic, and functional consequences of hypothermic storage alone, in experimental lung preservation.