Alpha-1 Antitrypsin Deficiency, Bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), Cystic Fibrosis, Emphysema, Pulmonary Fibrosis, Pulmonary Hypertension, Sarcoidosis
Conditions
Keywords
Lung Transplant, Emphysema, Chronic Obstructive Pulmonary Disease (COPD), Cystic Fibrosis, Pulmonary Fibrosis, Bronchiectasis, Sarcoidosis, Pulmonary Hypertension, Alpha-1 Antitrypsin Deficiency
Brief summary
The purpose of this research study is to learn about the safety of transplanting lungs obtained from non-heart-beating donors (NHBDs) 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 perfusion and ventilation is to learn how well the lungs work, and whether they are likely safe to transplant.
Interventions
PROCEDURETransplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) after ex-vivo perfusion w/ STEEN Solution™
After EVLP, lungs will be cooled in the circuit to room temperature, then flushed with cold Perfadex™, and taken to UNCH where they will have an ex-vivo CT scan. Lungs determined suitable will be offered to consented patients at UNC Hospitals and Duke University Medical Center 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 will be transplanted into recipients as per current clinical practice.
DEVICESTEEN Solution™
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.
Sponsors
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Vitrolife
XVIVO Perfusion
University of North Carolina, Chapel Hill
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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 transplant at UNC or Duke * Male or Female, 15 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.
Exclusion criteria
•Recipient fails to meet standard of care requirements for lung transplant, or decides not to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30 Day Mortality and Graft Survival | 30 Days | The primary objective evaluated for this study is recipient mortality and graft survival at 30 days post transplant. 30 day mortality and graft survival is used as a standard research assessment to evaluate post transplant outcomes. |
| Primary Lung Graft Dysfunction (PGD) | 24 and 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Length of Stay | Time to Discharge, up to 30 days | The length of ICU stay in days is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective. |
| Day 7 Ventilator/ECMO Status | 7 Days Post Transplant. | Participants' status at Day 7 defined as the following: mechanical ventilation, extra-corporeal membrane oxygenator (ECMO), or extubated. |
| Recipient Mortality at 12 Months | 12 months | Recipient mortality at 12 months post transplant is being evaluated as a secondary objective. |
| Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival | 12 Months | Bronchiolitis Obliterans Syndrome (BOS) free graft survival at 12 months is being used as a secondary outcome. |
Countries
United States
Participant flow
Pre-assignment details
Lungs were recovered from 35 NHBDs, 22 had EVLP. Two lung blocks were judged suitable, but not transplanted: No consented recipient available for #1, protocol time specifications could not be met for #2. As such, no subjects enrolled into EVLP arm.
Participants by arm
| Arm | Count |
|---|---|
| Ex-vivo Lung Perfusion With STEEN Solution™ Transplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) after ex-vivo perfusion w/ STEEN Solution™ and CT scan. | 0 |
| Lung Transplant From Conventional Brain-dead Organ Donor No experimental procedures will be carried out. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Ex-vivo Lung Perfusion With STEEN Solution™ | Lung Transplant From Conventional Brain-dead Organ Donor | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 12 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 12 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 20 Participants | 20 Participants |
| Region of Enrollment United States | — | 24 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 15 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 5 / 24 |
| other Total, other adverse events | 0 / 0 | 16 / 24 |
| serious Total, serious adverse events | 0 / 0 | 0 / 24 |
Outcome results
Primary
30 Day Mortality and Graft Survival
The primary objective evaluated for this study is recipient mortality and graft survival at 30 days post transplant. 30 day mortality and graft survival is used as a standard research assessment to evaluate post transplant outcomes.
Time frame: 30 Days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ex-vivo Lung Perfusion With STEEN Solution™ | 30 Day Mortality and Graft Survival | Alive | 0 Participants |
| Ex-vivo Lung Perfusion With STEEN Solution™ | 30 Day Mortality and Graft Survival | Deceased | 0 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | 30 Day Mortality and Graft Survival | Alive | 22 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | 30 Day Mortality and Graft Survival | Deceased | 2 Participants |
Primary
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.
Time frame: 24 and 72 hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ex-vivo Lung Perfusion With STEEN Solution™ | Primary Lung Graft Dysfunction (PGD) | Grade 0 | 0 Participants |
| Ex-vivo Lung Perfusion With STEEN Solution™ | Primary Lung Graft Dysfunction (PGD) | Grade 1 | 0 Participants |
| Ex-vivo Lung Perfusion With STEEN Solution™ | Primary Lung Graft Dysfunction (PGD) | Grade 2 | 0 Participants |
| Ex-vivo Lung Perfusion With STEEN Solution™ | Primary Lung Graft Dysfunction (PGD) | Grade 3 | 0 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Primary Lung Graft Dysfunction (PGD) | Grade 3 | 4 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Primary Lung Graft Dysfunction (PGD) | Grade 0 | 5 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Primary Lung Graft Dysfunction (PGD) | Grade 2 | 6 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Primary Lung Graft Dysfunction (PGD) | Grade 1 | 9 Participants |
Secondary
Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival
Bronchiolitis Obliterans Syndrome (BOS) free graft survival at 12 months is being used as a secondary outcome.
Time frame: 12 Months
Population: Excludes those who were deceased at Month 12
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lung Transplant From Conventional Brain-dead Organ Donor | Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival | BOS-Free | 17 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival | BOS | 2 Participants |
Secondary
Day 7 Ventilator/ECMO Status
Participants' status at Day 7 defined as the following: mechanical ventilation, extra-corporeal membrane oxygenator (ECMO), or extubated.
Time frame: 7 Days Post Transplant.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lung Transplant From Conventional Brain-dead Organ Donor | Day 7 Ventilator/ECMO Status | Mechanical Ventilator | 4 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Day 7 Ventilator/ECMO Status | ECMO | 1 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Day 7 Ventilator/ECMO Status | Extubated | 19 Participants |
Secondary
ICU Length of Stay
The length of ICU stay in days is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective.
Time frame: Time to Discharge, up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lung Transplant From Conventional Brain-dead Organ Donor | ICU Length of Stay | 6.91 Days | Standard Deviation 6.15 |
Secondary
Recipient Mortality at 12 Months
Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.
Time frame: 12 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lung Transplant From Conventional Brain-dead Organ Donor | Recipient Mortality at 12 Months | Alive | 19 Participants |
| Lung Transplant From Conventional Brain-dead Organ Donor | Recipient Mortality at 12 Months | Deceased | 5 Participants |