Ex-Vivo Lung Transplantation
Conditions
Brief summary
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.
Interventions
DEVICENPV-EVLP
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.
Sponsors
University of Alberta
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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: 1. Best ratio of the PaO2 to FiO2 of \< 300mmHg; 2. Pulmonary edema, defined as bilateral interstitial infiltrates without evidence of infection, detected on the last chest radiograph by the lung-transplantation physician assessing the donor; 3. Poor lung deflation or inflation during direct intraoperative visual examination at the donor site; 4. Donor age is ≥ 55 years; 5. Expected cold ischemic time \> 6 hours; 6. Blood transfusions ≥ 10 units; or 7. Donation after cardiac death (DCD), as defined by Maastricht category III (donor without a heartbeat and with cardiocirculatory death imminent after withdrawal of treatment) or category IV (cardiocirculatory death in a brain-dead donor). 5.2.2 Donor
Exclusion criteria
to NOT proceed with NPV-EVLP: 1. Donor lungs with established pneumonia; 2. Severe mechanical lung injury (i.e., contusions in more than one lobe) or trauma determined by chest x-ray, bronchoscopy, CT scan or visual inspection; or 3. Gross gastric aspiration within the lungs 4. Donor lungs have active infectious disease such as HIV, Hepatitis B, Hepatitis C, West Nile Virus (WNV), HTLV, or Syphillis (if this information not available at start of EVLP, it should be re-assessed prior to transplant). 5.3 POST-NPV-EVLP Donor Eligibility Criteria 5.3.1 Donor Inclusion Criteria to proceed with Transplant: 1. Surgeon must be satisfied with the clinical evaluation and appearance of the lungs; if not, reason for refusal must be documented; 2. Lungs show PaO2/FiO2 ratio ≥ 350mmHg; AND 3. Deterioration of less than 15% from baseline for physiological measurements pulmonary vascular resistance (PVR), dynamic compliance and peak inspiratory pressure. 5.3.2 Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Graft Dysfunction (PGD) Grade 3 in the first 72Hours | First 72Hours post-Transplant | 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. |
| Patient survival post transplantation at Day30 | Day30 post-Transplant | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU LOS | From admission to the ICU through to exact date of ICU Discharge (up to 30Days) | ICU length of stay (LOS) post-Transplant will be captured. |
| Hospital LOS | From date of Transplant through to exact date of Index Hospital Discharge (up to 6Months) | Index hospital length of stay (LOS) length of stay post-Transplant will be captured until D/C. |
| FEV1 | 6Months and 1Year | FEV1 results from spirometry efforts at 6Months and 1Year will be captured. |
| Quality of Life (SF-36) | 6Months and 1Year | Quality of Life measured by the 36-Item Short Form Survey (SF-36) at 6Months and 1Year will be captured. |
| Duration of Mechanical Ventilation post-Transplant | Time0 (ICU Admission post-Transplant) through to exact time of extubation post-Transplant | The duration of Mechanical Ventilation post-Transplant will be captured until extubation. |
| Primary Graft Dysfunction (PGD) Grades | Time0 (ICU Admission), Time24Hours (post-Transplant), Time48Hours (post-Transplant), and Time72Hours (post-Transplant) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoints as defined by the number of lung-related serious adverse events (SAEs) to Day30 | To Day30 post-Transplant | 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. |
Countries
Canada
Outcome results
None listed