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This project is focused on helping one of the most vulnerable patient populations in medicine, patients with end-stage chronic lung disease. Lung transplantation is the only cure for end-stage lung disease, however, due to the persistent shortage of donor organs, either due to low organ donation rates or unacceptable organs, only a minority of patients receive desperately needed lung transplants. Currently less than 30% of potential donated thoracic organs are being used for transplantation. The major causes for under utilization of donor thoracic organs are injury sustained by the lungs in trauma or emergency resuscitation or lungs that come from donors who are pronounced dead due to cardiac arrest (known as DCD donors). It has been hypothesized that these injuries may be reversible or repairable if there was an opportunity to evaluate and repair these organs outside of the body (ex-vivo), prior to transplantation. In fact, studies have shown that the use of normothermic Ex-Vivo Lung Perfusion (EVLP) has increased the rate of donor organ utilization at centers that have adopted the technology.
Current methodology for all clinically available EVLP devices uses Positive Pressure Ventilation (PPV). Researchers at the University of Alberta (UofA), however, have developed an EVLP device that will apply Negative Pressure Ventilation (NPV) to the lungs, as opposed to PPV, which is the most ideal mimicry of native lung physiology. The objective of this early feasibility safety trial is to show that the UofA developed NPV-EVLP device is acceptable in evaluating and improving the quality of marginal donor lungs compared to currently used EVLP devices, ultimately allowing for these types of donor lungs to be safely transplanted into patients on the lung transplant recipient waitlist.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Group | Experimental | After initial screening, appropriately obtained informed consent and confirmation of eligibility at time of transplant, those recipients (a total of 12 subjects) who agree to continue as participants will receive reconditioned marginal lungs should the lungs on the device meet acceptable criteria to proceed with clinical transplantation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NPV-EVLP | Device | Lungs deemed marginal based on standard lung donor criteria that meet study eligibility will be physiologically assessed during ex-vivo perfusion. NPV-EVLP of these lungs will be performed with the addition of numerous pre-determined additives. With respect to the decision of lung utilization post-EVLP, eligibility criteria listed in the Post-NPV-EVLP section of the trial will need to be met. Lungs will also be excluded if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon. |
| Measure | Description | Time Frame |
|---|---|---|
| Patient survival post transplantation at Day30 | The primary end point is a co-primary endpoint comparing patient survival rates post transplantation at Day30 (Outcome 1) and rates of Primary Graft Dysfunction (PGD) Grade 3 in the first 72 hours (Outcome 2) with success measured only if both endpoints are met. | Day30 post-Transplant |
| Primary Graft Dysfunction (PGD) Grade 3 in the first 72Hours | The primary end point is a co-primary endpoint comparing patient survival rates post transplantation at Day30 (Outcome 1) and rates of Primary Graft Dysfunction (PGD) Grade 3 in the first 72 hours (Outcome 2) with success measured only if both endpoints are met. | First 72Hours post-Transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Primary Graft Dysfunction (PGD) Grades | PGD scores will be assessed a Grade of 0, 1, 2 or 3 (per ISHLT Guidelines) at Time0 (ICU Admission), Time24Hours (post-Transplant), Time48Hours (post-Transplant), and Time72Hours (post-Transplant) with respect to PaO2/FiO2 ratios and presence/absence of radiographic infiltrates consistent with pulmonary edema. | Time0 (ICU Admission), Time24Hours (post-Transplant), Time48Hours (post-Transplant), and Time72Hours (post-Transplant) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety endpoints as defined by the number of lung-related serious adverse events (SAEs) to Day30 | Safety endpoints include the number of lung-related serious adverse events (SAEs) through to the Day30 follow-up after transplantation (T0) per subject. This endpoint will be defined to consist of the following serious adverse events: Acute rejection, Respiratory failure, Bronchial anastomotic complication, and Major pulmonary-related infection. |
5.2 PRE-NPV-EVLP Donor Eligibility Criteria
5.2.1 Donor MUST meet ANY ONE of the following Inclusion Criteria to proceed with NPV-EVLP:
5.2.2 Donor Exclusion Criteria to NOT proceed with NPV-EVLP:
5.3 POST-NPV-EVLP Donor Eligibility Criteria
5.3.1 Donor Inclusion Criteria to proceed with Transplant:
5.3.2 Donor Exclusion Criteria to proceed with Transplant:
5.4 Recipient Eligibility Criteria
5.4.1 Recipient Inclusion Criteria
5.4.2Recipient Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Jayan Nagendran, MD, PhD | Cardiac Surgeon, Director of Research, Associate Professor, University of Alberta | Principal Investigator |
| Darren Freed, MD, PhD | Cardiac Surgeon, Associate Professor, University of Alberta | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alberta Hospital | Edmonton | Alberta | T6G 2B7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33188221 | Derived | Buchko MT, Boroumand N, Cheng JC, Hirji A, Halloran K, Freed DH, Nagendran J. Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs. Nat Commun. 2020 Nov 13;11(1):5765. doi: 10.1038/s41467-020-19581-4. |
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Only aggregate and descriptive data of the experimental group vs the SOC arm will be shared in the form of publications.
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The purpose of this Phase I Early Feasibility Proof of Concept clinical trial will be to evaluate initial performance and safety of the NPV-EVLP device to assess and improve the function of marginal donor lungs. By nature, efficacy measures and outcomes of the device will also become evident from the results of this study.
This is a prospective, non-randomized, interventional trial, taking place solely at the University of Alberta Hospital/Mazankowski Alberta Heart Institute. Lungs deemed marginal, based on standard lung donor criteria that meet the study's eligibility criteria, will be assessed on our NPV-EVLP device to determine suitability for lung transplantation. Objective assessment of quality will be made while the lungs are on the device based on pre-determined functional parameters of lung physiology. Once a total of 12 sets of lungs are transplanted after using the device, safety will be determined by post-operative lung function and recipient survival.
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| ICU LOS | ICU length of stay (LOS) post-Transplant will be captured. | From admission to the ICU through to exact date of ICU Discharge (up to 30Days) |
| Hospital LOS | Index hospital length of stay (LOS) length of stay post-Transplant will be captured until D/C. | From date of Transplant through to exact date of Index Hospital Discharge (up to 6Months) |
| Duration of Mechanical Ventilation post-Transplant | The duration of Mechanical Ventilation post-Transplant will be captured until extubation. | Time0 (ICU Admission post-Transplant) through to exact time of extubation post-Transplant |
| FEV1 | FEV1 results from spirometry efforts at 6Months and 1Year will be captured. | 6Months and 1Year |
| Quality of Life (SF-36) | Quality of Life measured by the 36-Item Short Form Survey (SF-36) at 6Months and 1Year will be captured. | 6Months and 1Year |
| To Day30 post-Transplant |