Ex-Vivo Lung TransplantationUA NPV-EVLPNCT03293043
The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial
A study testing NPV-EVLP in people with Ex-Vivo Lung Transplantation, run by University of Alberta at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ex-Vivo Lung Transplantation
- What is being tested?
- NPV-EVLP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 11 Oct 2018to 22 Apr 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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:
- Best ratio of the PaO2 to FiO2 of < 300mmHg;
- 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;
- Poor lung deflation or inflation during direct intraoperative visual examination at the donor site;
- Donor age is ≥ 55 years;
- Expected cold ischemic time > 6 hours;
- Blood transfusions ≥ 10 units; or
- 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:
- Donor lungs with established pneumonia;
- 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
- Gross gastric aspiration within the lungs
- 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:
- Surgeon must be satisfied with the clinical evaluation and appearance of the lungs; if not, reason for refusal must be documented;
- Lungs show PaO2/FiO2 ratio ≥ 350mmHg; AND
- Deterioration of less than 15% from baseline for physiological measurements pulmonary vascular resistance (PVR), dynamic compliance and peak inspiratory pressure.
5.3.2 Donor Exclusion Criteria to proceed with Transplant:
- Lungs show a PaO2/FiO2 ratio of < 350mmHg;
- Greater than 15% functional deterioration across the following physiological parameters: PVR, dynamic compliance and peak inspiratory pressure;
- Donor lungs are positive for infectious disease such as HIV, Hepatitis B, Hepatitis C, West Nile Virus (WNV),HTLV, or Syphillis.
5.4 Recipient Eligibility Criteria
5.4.1 Recipient Inclusion Criteria
- Patients on our institution's waitlist requiring bilateral transplantation
- Male or Female 18 years of age or older
- Written informed consent provided.
5.4.2Recipient Exclusion Criteria
- Multi-organ recipient or re-transplant
- HIV, Hepatitis, or other infection that excludes subject from transplant in the study
- Subject is on hemodialysis or has chronic severe renal dysfunction
- Concurrent cardiac procedure
- Recipient is on Nova Lung, ECMO or on mechanical ventilation (CPAP and BiPAP not exclusionary)
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Ex-Vivo Lung Transplantation
- Being tested
- NPV-EVLP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPV-EVLPDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: NPV-EVLP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: First 72Hours post-Transplant
Secondary outcomes (6)
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.
Measured: Time0 (ICU Admission), Time24Hours (post-Transplant), Time48Hours (post-Transplant), and Time72Hours (post-Transplant)
ICU LOS
ICU length of stay (LOS) post-Transplant will be captured.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6Months and 1Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start11 Oct 2018
- Primary completion22 Apr 2021
- Study completion22 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ex-Vivo Lung TransplantationStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jayan Nagendran, MD, PhD, Principal investigator, Cardiac Surgeon, Director of Research, Associate Professor, University of AlbertaDarren Freed, MD, PhD, Principal investigator, Cardiac Surgeon, Associate Professor, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03293043
- Sponsor's protocol ID
- Pro00070552
- Acronym
- UA NPV-EVLP
- Status last verified
- Apr 2021
- First submitted
- 11 Sep 2017
- Last updated
- 26 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only aggregate and descriptive data of the experimental group vs the SOC arm will be shared in the form of publications.
Publications
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.
PubMed 33188221
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial
- ClinicalTrials.gov ID
- NCT03293043
- Acronym / sponsor ID
- UA NPV-EVLP / Pro00070552
- Conditions
- Ex-Vivo Lung Transplantation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 11 Oct 2018 (actual)
- Primary completion
- 22 Apr 2021 (actual)
- Study completion
- 22 Apr 2021 (actual)
- First posted
- 26 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Device: NPV-EVLPAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPV-EVLPLungs 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. | Device | Experimental Group |
Primary outcome
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.
6 secondary outcomes
Primary Graft Dysfunction (PGD) Grades
Time frame: Time0 (ICU Admission), Time24Hours (post-Transplant), Time48Hours (post-Transplant), and Time72Hours (post-Transplant)
ICU LOS
Time frame: From admission to the ICU through to exact date of ICU Discharge (up to 30Days)
Hospital LOS
Time frame: From date of Transplant through to exact date of Index Hospital Discharge (up to 6Months)
Duration of Mechanical Ventilation post-Transplant
Time frame: Time0 (ICU Admission post-Transplant) through to exact time of extubation post-Transplant
FEV1
Time frame: 6Months and 1Year
Quality of Life (SF-36)
Time frame: 6Months and 1Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
- Derived from this study: PubMed 33188221Buchko 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.
- Individual participant dataSharing planned: No. Only aggregate and descriptive data of the experimental group vs the SOC arm will be shared in the form of publications.
Related trials for Ex-Vivo Lung Transplantation
Active, not recruitingObservational study
An All Comers Registry For Normothermic Ex Vivo Lung Perfusion (EVLP) as Assessment of Donor Lungs for Transplant
Lung Transplant
Not yet recruiting
Comparison Between Two Medical Devices for the Reconditioning of Lungs Intended for Transplantation
Lung Transplant Surgery
RecruitingPhase 4
Combined Light, ExVivo, and Antivirals for Recipients of Lungs From HBV Donors
Hepatitis B Virus (HBV), Lung Transplant Recipient
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jayan Nagendran, MD, PhD principal investigator
Cardiac Surgeon, Director of Research, Associate Professor, University of Alberta
Darren Freed, MD, PhD principal investigator
Cardiac Surgeon, Associate Professor, University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NPV-EVLP in people with Ex-Vivo Lung Transplantation, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient survival post transplantation at Day30 (time frame: Day30 post-Transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03293043, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.