Inhaled Selective Pulmonary Vasodilators for Adult Lung Transplantation

Abstract

Purpose: Inhaled pulmonary vasodilators (iPVD) are commonly used in lung transplant recipients to mitigate the risk of primary graft dysfunction (PGD). While inhaled nitric oxide (iNO) is the gold standard for iPVD therapy, inhaled epoprostenol (Veletri®) has been introduced as a cost-conscious iNO-alternative without high-grade evidence. Thus, we conducted a clinical trial to primarily determine if inhaled epoprostenol is equivalent to iNO in the ability to modify grade 3 PGD after orthotopic lung transplantation. Methods: Our group has enrolled 200 lung transplant recipients in a triple-blinded (clinician, patient, statistician) randomized controlled trial conducted between June 2017-October 2020 (NCT03081052). Participants were first grouped into strata according to key clinical, prognostic features (Fig.1). Within each stratum, patients were assigned to receive either iNO or inhaled epoprostenol via 1:1 randomization. For our primary outcome analysis, to assess equivalency between the two treatment groups, we will calculate absolute and relative risk estimates and corresponding confidence intervals (CI). If the CI do not contain the margin of difference (15%), then we will conclude there is sufficient evidence that the risk of the primary outcome in each treatment group is similar. For each secondary outcome, we will construct univariable effect estimates and corresponding CI, which will allow for assessment of difference between treatment groups. In the case that patients have switched to the other treatment arm, we will perform the intent-to-treat (ITT) analysis without reclassifying treatment assignment. To verify ITT results, we will perform a per-protocol analysis. Endpoints: Primary. PGD-3 as defined by ISHLT 2016 criteria and an adjudicated PGD score at 72-hours after surgery. Secondary. Duration of postoperative mechanical ventilation, iPVD duration and cost, ICU and hospital lengths-of-stay, postoperative acute kidney Injury, and early postoperative mortality (in-hospital, 30-days, 90-days).