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Completed

NCT Number: NCT03293043

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

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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Key information

Conditions

Ex-Vivo Lung Transplantation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

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.

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. FEV1

    Time frame: 6Months and 1Year

    FEV1 results from spirometry efforts at 6Months and 1Year will be captured.

  6. 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.

Other outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

University of Alberta

Other

Registry information

Acronym: UA NPV-EVLP

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Sep 26, 2017
Registry last updated
Apr 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.