Although it missed its primary endpoint, the EXPAND trial has shown that use of a portable ex vivo lung perfusion system allowed successful transplantation of many lungs that were previously rejected by transplant centers.
The single-arm study, which was conducted at eight institutions in the United States, Germany and Belgium, was designed to evaluate the efficacy of using portable ex vivo lung perfusion with the Organ Care System (OCS) Lung (TransMedics Inc.).
The researchers included lungs from extended-criteria donors if they had at least one of the following: ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air of 300 mm Hg or less; expected ischemic time longer than 6 hours; donation after circulatory death; or donor age of at least 55 years. Eligible recipients included adults undergoing bilateral lung transplant.
A composite of patient survival at 30 days after transplant and absence of International Society for Heart and Lung Transplantation primary-graft dysfunction grade 3 (PGD3) within 72 hours after transplant served as the primary efficacy endpoint.
From 2014 to 2016, the researchers perfused, ventilated and assessed 93 lung pairs using the OCS Lung. Of these, 79 (87%) were transplanted. However, the primary endpoint was achieved in only 54% of patients, falling short of the prespecified objective performance goal of 65%. All but one patient were alive at 30 days after lung transplant, and the primary clinical driver for missing the performance goal was the relatively high proportion of patients with PGD3 within 72 hours after transplant (44%), the researchers noted.
Survival was also high at 6 and 12 months (94% and 91%, respectively).
In terms of safety, the mean number of lung graft-related serious adverse events, including respiratory failure and major pulmonary-related infection, was 0.3 events per patient.
To validate previous refusal status of donor lungs in the trial, the researchers assessed match run data from the United Network for Organ Sharing-Organ Procurement and Transplantation Network on the 66 donor lungs perfused on OCS Lung in the U.S. These donor lung pairs were refused by other transplant centers a mean of 35 times before acceptance in the EXPAND trial center.
Additionally, recipients of lungs in the trial reflected the real-world population of lung transplant recipients, according to the researchers. The mean lung allocation score was 42 and 23% of patients had idiopathic pulmonary fibrosis, 28% had secondary pulmonary hypertension and 48% underwent transplantation on cardiopulmonary bypass.
“The use of OCS Lung resulted in 87% of donor lungs being used, safely, from seldomly used lungs from extended-criteria donors and donors after circulatory death, with excellent survival outcomes up to 1 year of follow-up, few lung-graft-related serious adverse events and a low prevalence of bronchiolitis obliterans syndrome posttransplantation,” the researchers wrote. “The ability to optimize, functionally assess and safely use more lungs from these extended-criteria donors has the potential to substantially increase the number of viable donor lungs for transplantation globally.”
Longer follow-up is ongoing and a prospective registry has been developed to gather more evidence, they wrote. – by Melissa Foster
Disclosure: This study was funded by TransMedics Inc. Loor reports he has received grants from Maquet and United Therapeutics, and grants and nonfinancial support from TransMedics Inc.