Ghadimi, KamrouzCappiello, JhaymieCooter-Wright, MaryHaney, John CReynolds, John MBottiger, Brandi AKlapper, Jacob ALevy, Jerrold HHartwig, Matthew GINSPIRE-FLO Investigators2024-01-102024-01-102022-012168-62542168-6262https://hdl.handle.net/10161/29715<h4>Importance</h4>Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication.<h4>Objective</h4>To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO.<h4>Design, setting, and participants</h4>This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation.<h4>Interventions</h4>Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU).<h4>Main outcomes and measures</h4>The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome.<h4>Results</h4>A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes.<h4>Conclusions and relevance</h4>Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT03081052.https://creativecommons.org/licenses/by-nc/4.0INSPIRE-FLO InvestigatorsHumansNitric OxideEpoprostenolVasodilator AgentsPrognosisLung TransplantationAdministration, InhalationGraft RejectionAdultFemaleMaleJournal article