Lung Transplant
Conditions
Keywords
EVLP, Lung Transplantation
Brief summary
The purpose of this study is to see if adding a drug called Regadenoson to the EVLP circulation reservoir during perfusion of marginal donor lungs will help increase the likelihood that the donor lungs will become usable for transplantation.
Detailed description
Lung transplantation currently is one way to treat a variety of serious diseases and conditions such as emphysema, pulmonary fibrosis, and cystic fibrosis. Ischemia Reperfusion Injury (IRI) is a known problem that can happen during the first few days after a lung transplant. IRI can cause swelling of the lungs and low levels of oxygen. The most serious type of IRI can cause the transplanted lung to not work properly, it can even cause death. While new treatments and practices have been put into place to lower the chances of IRI, it is still a difficult problem to overcome after a lung transplant. Molecule called Adenosine 2A receptor (A2AR) have been studied in animals with IRI for many years. Some of these studies suggest that with the use of A2AR agonist, the chance of IRI may be lowered or prevented. Regadenoson is a selective A2AR agonist.
Interventions
DRUGRegadenoson
If the donor lungs are randomized the experimental arm, the administration of Regadenoson will be performed at each study site by a qualified medical professional. The donor lungs will be perfused with Regadenoson at a dosage of 1.44 microgram/kg/min (based on donor's weight) for a minimum of three hours and maximum of four hours, using a pediatric syringe pump into the EVLP circuit (XVIVO Perfusion System). The infusion will begin within 10 minutes of the start of the EVLP procedure. Once the EVLP is complete the lungs are re-flushed with Perfadex solution (removing the Steen™ solution and Regadenoson; standard for EVLP).
DRUGPlacebo
If the donor lungs are randomized to the Steen solution arm, the donor lungs will be perfused with placebo at a rate equivalent to the dosage of Regadenoson (1.44 microgram/kg/min), for a minimum of three hours and maximum of four hours, using the same pediatric syringe pump. The infusion will begin within 10 minutes of the start of the EVLP procedure.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
All study team members and subjects will be blinded to treatment assignment with the exception of the statisticians and investigational pharmacist preparing the study treatment.
Intervention model description
Randomization to the EVLP with placebo or EVLP with Regadenoson groups will be performed in a 1:2 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Donor Lung Inclusion Criteria for EVLP 1. At the time of clinical evaluation, the PaO2/FiO2 ≤ 300mm Hg OR 2. If the PaO2/FiO2 is \> 300mm hg and the donor has any one of more of the following donor risk factors: 1. Multiple blood transfusions 2. Pulmonary Edema detected via CXR, Bronchoscopy or palpation of the lungs 3. Donation after cardiac death donors 4. High risk donor history (example: asphyxia, hanging, drowning) Donor lung Inclusion Criteria for Transplant Suitability after EVLP 1. Delta PaO2 greater than 350 mmhg (measured with an FiO2 set at 1.0) at two consecutive time periods at 2, 3, or 4 hours of EVLP. 2. Stability or improvement of other lung function parameters during EVLP perfusion, such as PVR, compliance, or airway pressures. 3. Lungs clinically suitable for transplantation (e.g. without signs of significant contusions, edema, or secretion) in the opinion of the surgical investigator(s). Participant Inclusion Criteria 1. Subjects must be undergoing a single or bilateral lung transplantation for end-stage lung disease and thus meet all criteria to be listed. Single lungs are only allowable when initially placed as bilaterally block on EVLP circuit. 2. Male or female subject, 18 -75 years of age. 3. Subject agrees to accept EVLP perfused lungs. 4. Subjects must sign a study specific informed consent prior to study entry.
Exclusion criteria
Donor Lung
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lung Rehabilitation | 30 days | The primary endpoint is rehabilitation (yes, no) for marginal donor lungs that undergo ex-vivo perfusion using a lung box as assessed by the transplant surgeon and utilizing the Toronto Method clinical protocol. Rate of rehabilitation is defined as the proportion of sets of lungs that underwent EVLP with/without Regadenoson treatment and are determined to be eligible for implant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Lung Graft Dysfunction (PGD) Score | 72 hours | Primary graft dysfunction (PGD) is a clinical entity that reflects the development of early acute lung injury after lung transplantation. PGD severity is graded between 0 and 3 and it is measured at 6h, 12h, 24h, 48h and 72 hours after lung transplantation. A score of Score 0 means no PGD and 1-3 increasingly more severe. 3 is so severe requires ECMO support. |
| Intensive care unit length of stay | 8 weeks | Participants will be followed for the duration of hospital stay, an expected average of 8 weeks |
| Using of ECMO | 1 week | How often the patient will use ECMO due to lung infection after lung transplantation |
| Duration on ventilator post-Operative | 1 month | Will measure how long the patient use ventilator post-operation. |
| 12-month survival | 12 months | Patient survival 360 days after lung transplantation |
Countries
United States
Outcome results
None listed