New Protocol for Lung Transplants

Overseen By Carolyn Sidoti

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Disqualifiers: Unable to follow-up, No consent

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The study team developed an uncontrolled donation after circulatory death (uDCD) protocol that preserves lungs for just over 3 hours after death using positive end expiratory pressure (PEEP) and supplemental oxygen. The study will assess lung uDCD program safety by continuous review of operations/clinical records from each case activation and transplantation. Attrition outcomes include rates of initial and continued lung preservation, donation authorization, lung recovery, passing ex-vivo lung perfusion (EVLP) performance testing, and lung transplantation. Planned viability assessments also include macroscopic determination, radiology (X-ray), and fiber optic bronchoscopy before initiating EVLP. We expect \~50% of lungs assessed with EVLP will be transplanted to meet sustainability targets. Safety outcomes include the primary outcome, primary graft dysfunction (PGD) grade III at 72 hours, and secondarily survival one year after transplantation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the treatment Transplanting Lungs From Uncontrolled Donation After Circulatory Death?

Research shows that lung transplants from uncontrolled donors after circulatory death have similar short- and mid-term outcomes to those from traditional brain death donors, with comparable survival rates and complications. Additionally, a study reported excellent long-term results with a 5-year survival rate of 87.5% for recipients of these transplants. ^{1 2 3 4 5}

Is lung transplantation from uncontrolled donation after circulatory death safe?

Research shows that lung transplants from uncontrolled donors after circulatory death have similar safety outcomes to those from other types of donors. Studies found no significant differences in complications or survival rates, and some cases reported successful transplants with good recipient health after the procedure. ^{2 3 5 6 7}

How is the treatment of transplanting lungs from uncontrolled donation after circulatory death different from other lung transplant treatments?

This treatment is unique because it involves using lungs from donors who have died from circulatory causes, which are typically not used due to concerns about lung quality. The lungs are preserved using special techniques like alveolar recruitment maneuvers and ex vivo lung perfusion (a process that assesses and improves lung function outside the body), making them suitable for transplantation. ^{2 4 5 8 9}

Research Team

Stephen Wall, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for patients on the lung transplant waiting list who are willing to be part of a research study. They must be able to give consent themselves or through a surrogate and agree to follow-up for at least one year after receiving their transplant.

Inclusion Criteria

Willing to participate in the research study

Patients waiting for lung transplants

Exclusion Criteria

Unable to be followed for 1 year after transplantation

Unable to provide written informed consent to participate in the research (or designate a surrogate)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lung Preservation and Assessment

Lungs are preserved using PEEP and supplemental oxygen, followed by viability assessments including macroscopic determination, radiology, and fiber optic bronchoscopy before initiating EVLP.

3 hours

Transplantation and Immediate Post-Transplant Monitoring

Lungs are transplanted, and primary graft dysfunction (PGD) is assessed 72 hours post-transplant.

72 hours

Follow-up

Participants are monitored for survival and other outcomes up to one year after transplantation.

1 year

Treatment Details

Interventions

• Transplanting Lungs From Uncontrolled Donation After Circulatory Death

Trial Overview The trial tests a new protocol for preserving lungs from donors after death without heart function, using techniques like PEEP and supplemental oxygen. It aims to see how many preserved lungs pass quality checks and can be successfully transplanted.

Participant Groups

Group I: Lung uDCD Protocol Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

A new preservation method for lungs from uncontrolled donation after circulatory death (uDCD) showed excellent long-term outcomes, with 1-month, 1-year, and 5-year survival rates of 100%, 87.5%, and 87.5%, respectively, based on a study of 8 lung transplants from 9 evaluated donors.

The study reported a relatively low incidence of primary graft dysfunction (PGD) grade 3 at 25%, suggesting that the proposed preservation technique is effective in maintaining lung function prior to transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excellent long-term outcome with lungs obtained from uncontrolled donation after circulatory death. Suberviola, B., Mons, R., Ballesteros, MA., et al.[2023]

This case report demonstrates that lungs from an uncontrolled donor after circulatory death can be successfully procured and transplanted, even with challenges such as inhalation injury and prolonged ischemic times.

The recipient, a 26-year-old female with cystic fibrosis, showed positive outcomes post-transplant, surviving two years without signs of rejection, indicating that careful management can lead to successful transplantation from extended-criteria donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-criteria uncontrolled DCD donor for a fragile recipient: A case report about a challenging yet successful lung transplantation. Musso, V., Mendogni, P., Scaravilli, V., et al.[2023]

A study analyzing lung transplants from 239 brain death donors (DBD), 29 controlled donation after circulatory death donors (cDCD), and 14 uncontrolled donation after circulatory death donors (uDCD) found no significant differences in short- and mid-term outcomes, including graft dysfunction and survival rates.

The comparable outcomes across all donor types suggest that cDCD and uDCD can be viable sources for lung transplantation, potentially increasing the availability of suitable organs for patients in need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors. Campo-Cañaveral de la Cruz, JL., Crowley Carrasco, S., Tanaka, S., et al.[2022]

By accepting marginal donors and implementing a donation after circulatory death program, we have successfully expanded the pool of available donor lungs for transplantation, addressing the increasing demand.

Our results indicate that the outcomes from using marginal donors and lungs from donation after circulatory death are comparable to those from standard donors, which supports the safety and efficacy of these expanded criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation. Smail, H., Saxena, P., Wallinder, A., et al.[2018]

A new protocol was developed to successfully procure lungs from uncontrolled donors after circulatory death, with one case resulting in a successful transplantation after ex vivo lung perfusion (EVLP).

The recipient of the transplanted lungs, a 46-year-old male with cystic fibrosis, showed good health six months post-transplant, indicating that lungs can be viable for transplantation even after an extended warm ischemia period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion. Valenza, F., Citerio, G., Palleschi, A., et al.[2023]

The increase in organ donors from circulatory death significantly expands the available donor pool for transplants.

A new simplified and safe technique for lung flushing during recovery from donors after circulatory death aims to reduce warm ischemia time, which is crucial for improving transplant outcomes and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe Lung Flush Technique During Recovery From Donors After Circulatory Death. El-Sayed Ahmed, MM., Makey, IA., Landolfo, KP., et al.[2021]

This study successfully utilized uncontrolled donation after cardiac death (uDCD) for lung transplants, with a 16.7% use rate from consented donors, indicating a promising method to address lung shortages.

No severe primary graft dysfunction occurred post-transplant, and 30-day mortality was 0%, with four out of five patients surviving beyond 650 days, demonstrating both the safety and efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial lung transplantation experience with uncontrolled donation after cardiac death in North America. Healey, A., Watanabe, Y., Mills, C., et al.[2023]

The criteria for acceptable lung donors have been broadened, allowing for transplantation from donors who may not meet the ideal standards, based on specific patient and organ risk factors.

Ex vivo lung perfusion is emerging as a promising technique to recondition lungs that would typically be deemed unsuitable for transplant, potentially increasing the number of viable donor lungs available for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation and Management of the Potential Lung Donor. Courtwright, A., Cantu, E.[2022]

The study established a reproducible model of cardiac death in pigs, demonstrating significant deterioration in lung function post-cardiac death, with a marked decrease in oxygenation and pH levels, indicating potential challenges for organ viability.

Lung volume decreased significantly, and atelectasis (non-inflated lung tissue) increased after the cardiac death process, suggesting that the condition of lungs from uncontrolled donors after circulatory determination of death may be compromised for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deterioration of Lung Function in a Pig Model of Uncontrolled Cardiac Death. Safaee Fakhr, B., Dondossola, D., Cavenago, M., et al.[2018]

References

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

Excellent long-term outcome with lungs obtained from uncontrolled donation after circulatory death. [2023]

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

Extended-criteria uncontrolled DCD donor for a fragile recipient: A case report about a challenging yet successful lung transplantation. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation. [2018]

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

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safe Lung Flush Technique During Recovery From Donors After Circulatory Death. [2021]

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

Initial lung transplantation experience with uncontrolled donation after cardiac death in North America. [2023]

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

Evaluation and Management of the Potential Lung Donor. [2022]

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

Deterioration of Lung Function in a Pig Model of Uncontrolled Cardiac Death. [2018]