Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 20 for:    evlp

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03293043
Recruitment Status : Active, not recruiting
First Posted : September 26, 2017
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
University of Alberta

Tracking Information
First Submitted Date  ICMJE September 11, 2017
First Posted Date  ICMJE September 26, 2017
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE October 11, 2018
Estimated Primary Completion Date September 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03293043 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2019)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
  • 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 [ 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.
Current Other Pre-specified Outcome Measures
 (submitted: September 20, 2017)
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial
Official Title  ICMJE The University of Alberta Negative Pressure Ventilation Ex-Vivo Lung Perfusion (NPV-EVLP) Trial
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Ex-Vivo Lung Transplantation
Intervention  ICMJE Device: 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.
Study Arms  ICMJE 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.
Intervention: Device: NPV-EVLP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 20, 2017)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date September 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Exclusion Criteria to proceed with Transplant:

  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

5.4.1 Recipient Inclusion Criteria

  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.

5.4.2Recipient Exclusion 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03293043
Other Study ID Numbers  ICMJE Pro00070552
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Only aggregate and descriptive data of the experimental group vs the SOC arm will be shared in the form of publications.
Responsible Party University of Alberta
Study Sponsor  ICMJE University of Alberta
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account University of Alberta
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP