Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

Lung transplantation is the only treatment option that augments survival in patients with idiopathic pulmonary fibrosis (IPF). Despite several advancements in lung transplantation over the past three decades, long-term survival rates have remained low compared to other solid organ transplantations. The median survival after lung transplantation is only 5.8 years. Multiple factors account for the relatively low survival post-transplant, but chronic rejection resulting in obliterative bronchiolitis is a predominate cause. Further research is needed to develop medical therapeutic interventions that improve survival in IPF patients who undergo only single lung transplantation. Nintedanib, a novel tyrosine kinase inhibitor, exhibits antifibrotic properties via multiple mechanisms including the inhibition of the receptor tyrosine kinases platelet derived growth factor (PDGF) receptor, fibroblast growth factor (FGF) receptor, and vascular endothelial growth factor (VEGF) receptor. Several mediators of pulmonary fibrosis including VEGF, FGF, and transforming growth factor beta (TGF-β) have also been implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS), the most common type of chronic lung allograft rejection. Nintedanib is safe to continue until the time of lung transplantation and has not been shown to worsen perioperative outcomes in small case series, single center cohorts and our center's personal experience. The current practice in lung transplant medicine is to discontinue antifibrotic therapy after lung transplantation in IPF. In IPF patients who undergo single lung transplant, nintedanib therapy has the potential to preserve lung function in both the native fibrotic lung and the new lung allograft. The investigators propose a randomized and placebo-controlled single center pilot trial comparing nintedanib therapy plus usual care to usual care only in IPF patients after single lung transplant. The investigators hypothesize that in IPF subjects who undergo single lung transplantation the administration of nintedanib 150 mg twice daily in addition to usual transplant care will result in better preservation of lung function at 24 months.