The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial (UA NPV-EVLP)
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|ClinicalTrials.gov Identifier: NCT03293043|
Recruitment Status : Active, not recruiting
First Posted : September 26, 2017
Last Update Posted : September 6, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Ex-Vivo Lung Transplantation||Device: NPV-EVLP||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|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.
|Masking:||None (Open Label)|
|Primary Purpose:||Device Feasibility|
|Official Title:||The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial|
|Actual Study Start Date :||October 11, 2018|
|Estimated Primary Completion Date :||September 13, 2019|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: Experimental Group
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.
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.
- Patient survival post transplantation at Day30 [ Time Frame: 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.
- Primary Graft Dysfunction (PGD) Grade 3 in the first 72Hours [ Time Frame: 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.
- Primary Graft Dysfunction (PGD) Grades [ Time Frame: 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.
- ICU LOS [ Time Frame: 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 [ Time Frame: 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.
- Duration of Mechanical Ventilation post-Transplant [ Time Frame: 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.
- FEV1 [ Time Frame: 6Months and 1Year ]FEV1 results from spirometry efforts at 6Months and 1Year will be captured.
- Quality of Life (SF-36) [ Time Frame: 6Months and 1Year ]Quality of Life measured by the 36-Item Short Form Survey (SF-36) at 6Months and 1Year will be captured.
- Safety endpoints as defined by the number of lung‐related serious adverse events (SAEs) to Day30 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03293043
|University of Alberta Hospital|
|Edmonton, Alberta, Canada, T6G 2B7|
|Principal Investigator:||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|