Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs

Study Overview
=================
Brief Summary
-----------------
Human donor lungs that do not meet the standard clinical criteria for donor lung utilization but fit into the study inclusion criteria will be retrieved from the donor using current donor lung retrieval techniques.

Detailed Description
-----------------
These lungs will be brought to the study transplant center to be re-assessed by the transplant team. The lungs will be physiologically assessed during ex vivo perfusion with Steen Solution. Perfusion of these lungs will be performed using Steen solution with the addition of methylprednisolone, heparin and antibiotics. With respect to the decision of lung utilization those organs with a delta pO2 (Δ pO2 = Pulmonary vein pO2 - pulmonary artery pO2) during ex vivo perfusion assessment > 350mmHg, good lung compliance, and a favorable opinion of the transplant surgeon will be considered transplantable. Lungs will be excluded for transplantation: if the Δ pO2 is less than 350mmHg or if they demonstrate >10% deterioration in any of the following functional parameters: pulmonary vascular resistance (PVR), dynamic compliance or airway pressures. Lungs will also be excluded if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon.

Official Title
-----------------
Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs

Conditions
-----------------
Lung Transplant

Intervention / Treatment
-----------------
* Device: XPS™ with Steen Solution™


Participation Criteria
=================
Eligibility Criteria
-----------------
Recipient Inclusion/Exclusion Criteria The recipient inclusion/exclusion criteria apply to patients enrolled in the control or EVLP treatment arms. Recipient Inclusion Criteria Requires single or bilateral lung transplant. Male or Female, 18 years of age or older. Subject or Subject's Representative provides a legally effective informed consent. Recipient exclusion Criteria A recipient is HIV positive. A recipient has active Hepatitis. Investigator believes that the recipient has infection that excludes them from transplant in the study. To receive multi-organ transplant. Is on hemodialysis or has chronic severe renal dysfunction. Severe renal dysfunction is defined as a glomerular filtration rate of 29 or less (mL/min/1.73m2). Is to have planned concurrent cardiac procedures. A recipient is a re-transplant. (A re-transplant is defined as a recipient having the removal and transplant of a previously transplanted lung. A recipient with a previously single lung transplant is eligible to enroll in the trial if it is for the other lung and within 6 months of previous transplant.) A recipient is on Nova Lung, ECMO, or on mechanical ventilation. (CPAP and BIPAP are not exclusionary) Donor Inclusion/Exclusion Criteria for EVLP Assessment Donor Inclusion Criteria The Donor lung must meet the following criteria to proceed with EVLP: At the time of the clinical evaluation , the PaO2/FiO2 ≤ 300mmHg Or If PaO2/FiO2 > 30mmHg and the donor has any one or more of the following donor risk factors: Multiple blood transfusions. Pulmonary edema detected via CXR, bronchoscopy or palpation of lungs. Donation after circulatory death donors. Investigator evaluation of donor lung as unsuitable for standard criteria for lung transplant. List reason for unsuitable determination. Donor Exclusion Criteria Lung has significant pneumonia and/or persistent purulent secretions on bronchoscopy as determined by investigator. Donor has known significant aspiration of gastric contents within the lung. Donor lung has significant mechanical lung injury or trauma determined by chest x-ray, bronchoscopy, CT Scan or visual inspection. Donor lung has active infectious disease such as HIV, Hepatitis B or C, HTLV or Syphilis. Note: This information is not available at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant. Donor Inclusion/Exclusion Criteria for Transplant Suitability after EVLP Donor Inclusion Criteria for Transplant Suitability Surgeon must be clinically satisfied with the lung evaluation (i.e.) overall improvement, if not, the reason for refusal must be listed. Stability or improvement of other lung function parameters during EVLP perfusion - PVR, Compliance, Airway Pressures. Two delta PO2 greater than 350 mmHg, if two delta PO2 mm Hg are not met than three out of four of the following parameters must be present: One delta PO2 of > 350 or absolute PO2 of > 400. Chest x-ray findings with absence or improvement of pulmonary edema/infiltrates Compliance static (greater than 35 single and greater than 60 for a double) Absence of consolidation by palpation Donor Exclusion Criteria for Transplant Suitability after EVLP All delta PO2 (s) are less than 350 mmHg (measured with a FiO2 set at 1.0) or all absolute PO2s are less than 400. Overall greater than 10-15% Functional deterioration of other lung function across all parameters (PVR, Compliance, PawP) with chest x-ray findings showing deterioration. Donor lung positive for infectious diseases such as HIV, Hepatitis B or C, or Syphilis. Note: This information is not available until at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVLP Group<br>EVLP Group are those recipient lung transplant patients that received donor lungs that had been placed on the XPS™ with Steen Solution™ and undergone ex-vivo lung perfusion before being transplanted. | Device: XPS™ with Steen Solution™<br>* The XPS™ System is an integrated cardiac bypass system comprised of various components such as a Maquet CardioHelp centrifugal pump (K102726), the HicoVariotherm Heater/Cooler, the Hamilton C2 ICU (intensive care unit) pressure- controlled ventilator (K092148), the perfusate gas monitors, and the display monitors. The XPS™ System is responsible for housing the organ for preservation, providing the normothermic environment, and perfusing the organ with the STEEN Solution™. Donor lungs that meet inclusion criteria are placed on the XPS™ and rewarmed and perfused with STEEN Solution™ and ventilated for 3-6 hours. If the lungs meet transplant suitability, they are cooled down and transplanted into a consented recipient that meet's trial criteria.<br>* Other names: ex vivo lung perfusion;|
| No Intervention: Control Group<br>Control Group are those recipient lung transplant patients that receive donor lungs via conventional transplant. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PAS Study Primary Endpoint | The primary end point is a co-primary endpoint comparing survival rates and rates of grade 3 PGD at 72 hours with success if and only if both endpoints are met. Treatment Group (T) = EVLP transplant subjects Control Group (C) = standard transplant subjects Co-Primary Endpoints: Endpoint #1: Survival of T is non-inferior to C Ho: C - T ≥ M1 (T is inferior to the control by M1 or more) Ha: C - T < M1 (T is inferior to the control by less than M1) where M1 = 0.12 Endpoint #2: Rate of grade 3 PGD at 72 hours for T is non-inferior to the rate for C Ho: C - T ≥ M2 Ha: C - T < M2 where M2 = 0.12 | 3 Years | 
| PMA Study Primary Endpoint | The primary end point is non-inferiority of the 3-year survival rate of the EVLP group as compared to 3-year survival rate of the control group. Ho: C - T ≥ M3 (T is inferior to the control by M3 or more) Ha: C - T < M3 (T is inferior to the control by less than M3) where M3 = 0.12 | 72hrs and Survival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PMA Secondary Endpoints | Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity The PMA secondary endpoints are as follows: FEV1 at 3 mos, 6 mos, 9 mos, and 1 yr PGD score at 24 and 48 hrs ICU LOS Hospital LOS Use of ECMO due to lung function post transplant Duration of mechanical ventilation post transplant Quality of Life and functional status at one year | 3 Years | 
| PAS Secondary Endpoint: | Quality of Life measured by functional status, physical capability, and employment limitations. Episodes of rejection per UNOS registry FEV1 at 1, 2, 3, 4, and 5 years | 5 Years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lung Transplant, Transplantation Lung