The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial

NCT ID: NCT03293043

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2021-04-22

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.

Conditions

Ex-Vivo Lung Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

NPV-EVLP

Intervention Type: 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.

Interventions

NPV-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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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).

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.

1. Patients on our institution's waitlist requiring bilateral transplantation

2. Male or Female 18 years of age or older

3. Written informed consent provided.

Exclusion Criteria

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

1. Lungs show a PaO2/FiO2 ratio of < 350mmHg;

2. Greater than 15% functional deterioration across the following physiological parameters: PVR, dynamic compliance and peak inspiratory pressure;

3. 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

1. Multi-organ recipient or re-transplant

2. HIV, Hepatitis, or other infection that excludes subject from transplant in the study

3. Subject is on hemodialysis or has chronic severe renal dysfunction

4. Concurrent cardiac procedure

5. Recipient is on Nova Lung, ECMO or on mechanical ventilation (CPAP and BiPAP not exclusionary)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jayan Nagendran, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardiac Surgeon, Director of Research, Associate Professor, University of Alberta

Darren Freed, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardiac Surgeon, Associate Professor, University of Alberta

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 33188221 (View on PubMed)

Other Identifiers

Pro00070552

Identifier Type: -

Identifier Source: org_study_id