Lung transplantation: lung ischemia repferfusion injury and primary graft dysfunction primary graft dysfunction / pulmonary failure after lung transplantation
Conditions
Interventions
The intervention under investigation is the administration of an extra or additional retrograde flush (ARF) of donor lungs immediately prior to implantation in the recipient using Perfadex® Plus. 
Perfadex® Plus is the standard flush fluid already clinically used worldwide during lung procurement in the donor and is not under investigation in this study. The retrograde flushing technique used i
the 2024 American Association for Thoracic Surgery expert consensus document. 
Recipients will be randomized for their allocated donor lungs either to receive the ARF or to be used as a control. If the donor lung of a recipient is allocated as control no intervention will take p
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Adult >18 yearWilling, volunatarily, and able to sign informed consent (legally able to give informed consent (has adequate decision-making capacity))On the transplant list for bilateral lung transplantation.Donor lungs definitively accepted for implantation.
Exclusion criteria
Exclusion criteria: BMI >30 at the time of being listed on the waiting list (for lung transplantation)Mean pulmonary artery pressure of >40 mmHg at the time of being listed on the waiting listBridged to transplant with extracorporeal life support (ECLS) and/or mechanical ventilationUndergoing a re-transplantationRequiring a donor lung(s) which has undergone size reduction (including a lobar transplant)Allocated lungs having undergone ex vivo lung perfusion (EVLP)Unable to give informed consent Right sided heart failure with a cardiac index of <2.0 L/min/ m² as measured during right heart catheterization.Involved in a competing study, for instance the abdominal NRP (normothermic regional perfusion) trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate if additional retrograde flushing of lung allografts with Perfadex® Plus solution immediately prior to implantation leads to improved short-term outcome in the first 72 hours following lung transplantation in low- to medium risk recipients. The ARF will be approximately 1.5L of the Perfadex® Plus solution for each lung, or the volume of flush required for the ARF effluent to run clear.TThe primary outcome measure will be ‘Extubation at 24 hours’ following lung transplantation, as a dichotomous outcome. These 24 hours start at the time of ICU admission after completion of the lung transplantation procedure. This is an objective and clinically relevant outcome reflecting early graft function in the recipient. Patients on a ventilator are not always extubated as soon as clinically possible. For a number of reasons extubation may be deferred for several hours. One such example may be because an intensive care unit (ICU) delays extubation of a patient until routine ‘day’ hours, avoiding out-of-hours extubation, or because an ICU physician is not immediately available, thus passing the 24-hours timepoint. Therefore, ‘minimal’ ventilator settings compatible with extubation (see section 8.3 of the study protocol) will also be classified as achievement of the primary outcome. | — |
Secondary
| Measure | Time frame |
|---|---|
| A hierarchical composite endpoint will be used with the ‘win ratio’ approach. The composite clinical outcomes to be used in the win ratio will be: ‘any PGD grade 3 within 72 hours following transplant’, ‘ventilator-free hours at 72 hours post-transplant’ and ‘P/F ratio within the first 24 hours post-transplant’. The win ratio approach allows for the priority or clinical importance of a number of composite outcomes to be taken into account and can analyze composites of different types of outcomes, such as time-to-event analysis and continuous and/or categorical data. We further aim to identify the presence and quantify the number of donor neutrophils at the start and end of the ARF of donor lungs prior to surgical implantation, so when the lungs are still outside of the patient. We also aim to perform point-of-care flow cytometry analysis of the donor neutrophils to identify any differences in the neutrophil phenotype present in the flush and any association with the donor procedure: donation after circulatory death (DCD) or donation following brain death (DBD). A further secondary outcome will include medium-term outcome measures of lung function and graft-rejection of patients in both groups: We will record and compare the forced expiratory volume in 1 second (FEV1) between patients in the intervention group and patients in the control group. The FEV1 is measured as part of the standard care and monitoring of patients following lung transplantation. We will not perform extra lung function tests outside of those done as standard of care/ monitoring. Episodes of lung-allograft rejection will be recorded and are defined as persistent lung function decline (FEV1) >20% from baseline post-transplant more than 3 weeks in the post-transplant period. | — |
Countries
Belgium, Netherlands
Contacts
Public ContactS.A. Braithwaite
Universitair Medisch Centrum Utrecht
Outcome results
None listed