Normothermic <i>ex vivo</i> Lung Perfusion (NOVEL) as an Assessment of Extended/Marginal Donor Lungs: A Prospective Multi-Center Clinical Trial

Abstract

Background: Ex vivo lung perfusion (EVLP) allows re-evaluation of lungs initially deemed not viable for transplantation. However, the mid- and long-term outcomes after transplanting EVLP-screened lungs in a multicenter setting are still unknown. Methods: This was a multicenter, prospective, nonrandomized clinical trial. Donor lungs initially deemed not suitable (n=208) were re-evaluated on EVLP. Lungs that met quality criteria after EVLP were transplanted (n=110). Transplants performed at the same institutions using standard-criteria lungs were enrolled as controls (n=116). Primary outcomes included grade 3 primary graft dysfunction (PGD) 72 hours post-transplant and 1- and 3-year survival. Secondary outcomes included PGD 24 and 48 hours post-transplant, pulmonary function, bronchiolitis obliterans syndrome (BOS) and quality of life. Findings: Half of the lungs placed on EVLP were transplanted (102/208, 49%). The incidence of severe PGD 72 hours post-transplant was not significant different from controls (13·6% vs 6·9%, p=0.09). Moreover, survival was not significantly different 1- and 3-years post-transplant (EVLP, 86%; control, 93%; p=0·09 and EVLP, 68%; control, 77%; p=0·14, respectively). There were also no differences in pulmonary function or the incidence of BOS up to 3 years post-transplant, and no difference in quality-of-life measures 1- and 3-years post-transplant. Interpretation: In this multicenter study, recipients of lungs that were re-evaluated on EVLP and deemed suitable for transplant had similar outcomes as a recipients of a standard lung transplant. EVLP offers the opportunity to screen donated lungs initially considered high risk and can safely increase the availability of transplantable lungs without compromising outcomes. Clinical Trial Registration Details: Registered on ClinicalTrials.gov (NCT 01365429). Funding Information: XVIVO Perfusion, Inc. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by each transplant center’s Institutional Review Board and the FDA. Participants provided written informed consent to participate in this study.