TY - JOUR
T1 - A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs
AU - Hartwig, Matthew G.
AU - Klapper, Jacob A.
AU - Poola, Nagaraju
AU - Banga, Amit
AU - Sanchez, Pablo G.
AU - Murala, John S.
AU - Potenziano, Jim L.
N1 - Funding Information:
This study and the journal’s Rapid Service Fee were funded by Mallinckrodt Pharmaceuticals.
Funding Information:
This study and the journal’s Rapid Service Fee were funded by Mallinckrodt Pharmaceuticals. Professional writing and editorial support were provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of the authors and was funded by Mallinckrodt Pharmaceuticals. All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors were involved in the conception and design of the study, data collection and analysis, writing of the manuscript, and approval of the final version for submission. Matthew Hartwig is a consultant for BioMed Innovations and Paragonix; has received grant/research support from Mallinckrodt Pharmaceuticals, Transmedics, and BioMed Innovations; and has other/educational relationships with Intuitive. Jacob Klapper has no financial relationships with commercial interests to disclose. Nagaraju Poola is a former employee of Mallinckrodt Pharmaceuticals. Amit Banga has no financial relationships with commercial interests to disclose. Pablo G. Sanchez has no financial relationships with commercial interests to disclose. John S. Murala has no financial relationships with commercial interests to disclose. Jim L. Potenziano is a former employee of Mallinckrodt Pharmaceuticals. The study was conducted in compliance with the principles of the Declaration of Helsinki of 1964 and its later amendments and the Declaration of Istanbul, and was in strict compliance with the ISHLT guidelines for transplant ethics. The lungs procured for this study did not meet the requirement for human subjects and were exempt from Institutional Review Board (IRB) review. Each investigator obtained an IRB exemption from their institution before initiating the study, including the Duke University Health System IRB, the University of Pittsburgh IRB, and the University of Texas Southwestern Medical Center IRB. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Funding Information:
Professional writing and editorial support were provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of the authors and was funded by Mallinckrodt Pharmaceuticals.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/3
Y1 - 2023/3
N2 - Introduction: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. Methods: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). Results: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0–3.5 [0, 7]) vs. P (0–2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. Conclusions: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.
AB - Introduction: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. Methods: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). Results: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0–3.5 [0, 7]) vs. P (0–2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. Conclusions: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.
KW - Donor lungs
KW - Ex vivo lung perfusion
KW - Lung transplant
KW - Nitric oxide
KW - Transplantation suitability
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U2 - 10.1007/s41030-022-00209-5
DO - 10.1007/s41030-022-00209-5
M3 - Article
C2 - 36510099
AN - SCOPUS:85143818517
SN - 2364-1754
VL - 9
SP - 151
EP - 163
JO - Pulmonary Therapy
JF - Pulmonary Therapy
IS - 1
ER -