Lung Preservation
Conditions
Brief summary
A prospective, international, multi-center, randomized controlled trial comparing preservation of donor lungs using OCS-Lung perfusion device (Treatment Group) to cold flush and storage (Control Group).
Interventions
DEVICEOCS Lung
OCS Lung will be used to preserve the donor lungs (Treatment Group).
DEVICECold flush and storage
Donor lungs will preserved using standard cold flush and storage
Sponsors
TransMedics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Registered primary double-lung transplant candidate * Age \> or equal to 18 * Signed: 1) written informed consent document and 2) authorization to use and disclose protected health information
Exclusion criteria
* Prior solid organ or bone marrow transplant * Single lung recipient * Multiple organ transplant recipient * Chronic use of hemodialysis or diagnosis of chronic renal insufficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation. | Day 30 after transplantation | This composite is a single outcome measure. Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation | 72 hours after transplantation | Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome. |
| Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation | 72 hours after transplantation | Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome. |
| Patient Survival at Day 30 | Day 30 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint: Lung Graft-related Serious Adverse Events (LGRSAEs) Through 30-days Post-transplant Per Subject | 30 days post-transplant | An LGRSAE event is defined as the occurrence of any of the following four categories of adverse events that are also serious; acute rejection, respiratory failure, bronchial anastomotic complication, and major pulmonary-related infection. |
| Long-term Survival: 24-month Survival | 24 months | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OCS Lung (Treatment Group) The OCS Lung, which is a portable, integrated platform designed to maintain adult donor lungs in a normothermic state through continuous normothermic perfusion and ventilation, will be used to preserve and transport donor lungs.
OCS Lung: OCS Lung will be used to preserve the donor lungs (Treatment Group). | 151 |
| Cold Flush and Storage (Control Group) Donor lungs will be preserved using cold flush and storage (control group)
Cold flush and storage: Donor lungs will preserved using standard cold flush and storage | 169 |
| Total | 320 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 20 | 26 |
| Overall Study | Donor lungs turned down | 1 | 0 |
| Overall Study | Protocol Violation | 9 | 4 |
Baseline characteristics
| Characteristic | OCS Lung (Treatment Group) | Cold Flush and Storage (Control Group) | Total |
|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 13.1 | 50.0 years STANDARD_DEVIATION 13.6 | 50.2 years STANDARD_DEVIATION 13.3 |
| Donor Smoking History in Past 6 Months | 27 Participants | 27 Participants | 54 Participants |
| Final PaO2:FiO2 (mm Hg) | 438.5 mm Hg STANDARD_DEVIATION 80 | 431.7 mm Hg STANDARD_DEVIATION 73.8 | 434.9 mm Hg STANDARD_DEVIATION 76.7 |
| Recipient BMI | 23.2 kg/m^2 STANDARD_DEVIATION 4.6 | 23.0 kg/m^2 STANDARD_DEVIATION 4.1 | 23.1 kg/m^2 STANDARD_DEVIATION 4.3 |
| Recipient Lung Allocation Score | 50.8 score on a scale STANDARD_DEVIATION 20.9 | 47.9 score on a scale STANDARD_DEVIATION 18.7 | 49.3 score on a scale STANDARD_DEVIATION 19.8 |
| Recipient Transplant Indication COPD | 46 Participants | 52 Participants | 98 Participants |
| Recipient Transplant Indication Cystic Fibrosis | 31 Participants | 40 Participants | 71 Participants |
| Recipient Transplant Indication Idiopathic Pulmonary Hypertension | 13 Participants | 6 Participants | 19 Participants |
| Recipient Transplant Indication Other | 8 Participants | 6 Participants | 14 Participants |
| Recipient Transplant Indication Pulmonary Fibrosis | 49 Participants | 57 Participants | 106 Participants |
| Recipient Transplant Indication Sarcoidosis | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Female | 74 Participants | 67 Participants | 139 Participants |
| Sex: Female, Male Male | 79 Participants | 102 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 151 | 27 / 169 |
| other Total, other adverse events | 125 / 150 | 141 / 169 |
| serious Total, serious adverse events | 83 / 150 | 107 / 169 |
Outcome results
Primary
A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation.
This composite is a single outcome measure. Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome.
Time frame: Day 30 after transplantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation. | 112 Participants |
| Cold Flush and Storage (Control Group) - Per Protocol | A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation. | 116 Participants |
| OCS Lung (Treatment Group) - ITT | A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation. | 112 Participants |
| Cold Flush and Storage (Control Group) - ITT | A Composite of Patient Survival at Day 30 Post Transplantation, and Absence of International Society for Heart & Lung Transplantation (ISHLT) Primary Graft Dysfunction (PGD3) Grade 3 Within the First 72 Hours Post-transplantation. | 119 Participants |
p-value: 0.004Wald Method
p-value: 0.06Wald Method
Secondary
Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation
Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome.
Time frame: 72 hours after transplantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation | 3 Participants |
| Cold Flush and Storage (Control Group) - Per Protocol | Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation | 6 Participants |
| OCS Lung (Treatment Group) - ITT | Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation | 7 Participants |
| Cold Flush and Storage (Control Group) - ITT | Participants With International Society for Heart & Lung Transplantation (ISHLT) PGD Grade 3 at 72 Hours Post-transplantation | 7 Participants |
p-value: 0.0003Wald Method
p-value: 0.027Wald Method
Secondary
Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation
Primary graft dysfunction is graded on a scale of 0 to 3 according to the 2005 ISHLT PGD grading consensus. Grade 0 is considered the least severe and grade 3 is considered a more severe outcome.
Time frame: 72 hours after transplantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation | 16 Participants |
| Cold Flush and Storage (Control Group) - Per Protocol | Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation | 13 Participants |
| OCS Lung (Treatment Group) - ITT | Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation | 22 Participants |
| Cold Flush and Storage (Control Group) - ITT | Participants With ISHLT PGD Grade 2 or 3 at 72 Hours Post-transplantation | 14 Participants |
p-value: 0.118Wald Method
p-value: 0.389Wald Method
Secondary
Patient Survival at Day 30
Time frame: Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | Patient Survival at Day 30 | 135 Participants |
| Cold Flush and Storage (Control Group) - Per Protocol | Patient Survival at Day 30 | 165 Participants |
| OCS Lung (Treatment Group) - ITT | Patient Survival at Day 30 | 142 Participants |
| Cold Flush and Storage (Control Group) - ITT | Patient Survival at Day 30 | 168 Participants |
Other Pre-specified
Long-term Survival: 24-month Survival
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | Long-term Survival: 24-month Survival | 121 Participants |
| Cold Flush and Storage (Control Group) - Per Protocol | Long-term Survival: 24-month Survival | 139 Participants |
| OCS Lung (Treatment Group) - ITT | Long-term Survival: 24-month Survival | 127 Participants |
| Cold Flush and Storage (Control Group) - ITT | Long-term Survival: 24-month Survival | 142 Participants |
Other Pre-specified
Primary Safety Endpoint: Lung Graft-related Serious Adverse Events (LGRSAEs) Through 30-days Post-transplant Per Subject
An LGRSAE event is defined as the occurrence of any of the following four categories of adverse events that are also serious; acute rejection, respiratory failure, bronchial anastomotic complication, and major pulmonary-related infection.
Time frame: 30 days post-transplant
Population: This analysis was done on the safety population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| OCS Lung (Treatment Group) - Per Protocol | Primary Safety Endpoint: Lung Graft-related Serious Adverse Events (LGRSAEs) Through 30-days Post-transplant Per Subject | 0.23 events per participant |
| Cold Flush and Storage (Control Group) - Per Protocol | Primary Safety Endpoint: Lung Graft-related Serious Adverse Events (LGRSAEs) Through 30-days Post-transplant Per Subject | 0.28 events per participant |
p-value: <0.0001t-test, 2 sided