Phase 2 Study of Ex-vivo Perfusion and Ventilation of Lungs to Assess Transplant Suitability

Study Overview
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Brief Summary
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The purpose of this research study is to perfect the technique of EVLP and learn about the safety of transplanting lungs that have been ventilated (attached to a breathing machine or ventilator to deliver oxygen) and perfused with a lung perfusion solution (Steen solution™, made by Vitrolife). This ventilation and perfusion will be done outside the body (ex-vivo) in a modified cardiopulmonary bypass circuit (the kind of device used routinely during most heart surgeries). The purpose of performing ex-vivo lung perfusion and ventilation (EVLP) is to learn how well the lungs work, and whether they are likely safe to transplant.

Official Title
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Phase 2 Study of Ex-vivo Perfusion and Ventilation of Lungs to Assess Transplant Suitability

Conditions
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Emphysema, Chronic Obstructive Pulmonary Disease (COPD), Cystic Fibrosis, Pulmonary Fibrosis, Bronchiectasis, Sarcoidosis, Pulmonary Hypertension, Alpha-1 Antitrypsin Deficiency

Intervention / Treatment
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* Device: Steen Solution™
* Other: Conventional Lung Transplant


Participation Criteria
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Eligibility Criteria
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Lung Recipient Inclusion Criteria: A recipient must meet the following requirement to enroll into the study: Requires a single or bilateral lung transplant and is listed for lung transplant at UNC. Male or Female, 18 years of age or older. Subject or Subject's Representative provides a legally effective informed consent. Recipient does not have HIV, active Hepatitis or is colonized with Burkholderia cepacia. Potential subjects who have undergone previous lung transplants and meet all other inclusion criteria are eligible for study participation. Lung Recipient Exclusion Criteria: Recipient fails to meet standard of care requirements for lung transplant, or decides not to participate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVLP with STEEN Solution™<br>The perfusion of the lungs will be performed using STEEN Solution™ and then physiologically assessed. Lungs deemed suitable will be transplanted after Ex-vivo Perfusion w/ STEEN Solution™. | Device: Steen Solution™<br>* This solution is a buffered dextran and albumin-containing extracellular perfusate with an optimal colloid osmotic pressure developed specifically for extra-corporeal perfusion of lungs. After EVLP, lungs will be cooled in the circuit to room temperature, then flushed with cold Perfadex™ and taken to UNC Hospitals (UNCH) where they will have an ex-vivo CT scan. Lungs determined suitable will be offered to consented patients at UNCH based on Lung Allocation Score. Lungs not considered for transplantation may be subjected to different experiments but are not to be a part of this research study. In summary, lungs with good and stable function during EVLP with Steen Solution™ will be transplanted into recipients as per current clinical practice.<br>|
| Active Comparator: Conventional Lung transplant<br>No experimental procedures will be carried out. Lungs from conventional brain-dead organ donors will be used for transplant. | Other: Conventional Lung Transplant<br>* No experimental procedures will be carried out. Lungs from conventional brain-dead organ donors will be used for transplant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30 Day Mortality | The primary objective evaluated for this study is recipient mortality at 30 days post transplant. 30 day mortality is used as a standard research assessment to evaluate post transplant outcomes. | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Lung Graft Dysfunction (PGD) | Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity and mortality after lung transplantation. Grade 0: PaO2*/FIO2** > 300 with normal chest radiograph; Grade 1: PaO2/FIO2 > 300 with diffuse infiltrates on the chest radiograph; Grade 2: PaO2/FIO2 between 200 and 300; Grade 3: PaO2/FIO2 < 200. * partial pressure of oxygen in the arterial blood (PaO2) ** fraction of inspired oxygen inspired oxygen fraction (FIO2) | 24 and 72 hours post transplant. | 
| ICU Length of Stay | The length of ICU stay is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective. | Time to Discharge. | 
| Day 7 Ventilator/ECMO Status | 7 days ventilator or extra-corporeal membrane oxygenator (ECMO free are being evaluated as secondary objectives. | 7 Days Post Transplant. | 
| Recipient mortality at 12 months. | Recipient mortality at 12 months post transplant is being evaluated as a secondary objective. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Transplant, Emphysema, Chronic Obstructive Pulmonary Disease (COPD), Cystic Fibrosis, Pulmonary Fibrosis, Bronchiectasis, Sarcoidosis, Pulmonary Hypertension, Alpha-1 Antitrypsin Deficiency