From McMaster University and St. Joseph's Healthcare, Hamilton, ON, Canada (M.K.); the University of Washington, Seattle (G.R.); the National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, and the National Heart and Lung Institute, Imperial College, London (A.U.W.); Medizinische Klinik und Poliklinik V, University of Munich and Asklepios Klinik München–Gauting, German Center for Lung Research, Munich (J.B.), and Boehringer Ingelheim International, Ingelheim (B.S., M.Q., S.S.) — both in Germany; Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome (L.R.); and Weill Cornell Medicine, New York (F.J.M.).
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BackgroundNintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). A subgroup analysis of a previously published trial suggested that sildenafil may provide benefits regarding oxygenation, gas exchange as measured by the diffusion capacity of the lungs for carbon monoxide (DlCO), symptoms, and quality of life in patients with IPF and severely decreased DlCO. That idea was tested in this trial.MethodsWe randomly assigned, in a 1:1 ratio, patients with IPF and a DlCO of 35% or less of the predicted value to receive nintedanib at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times daily (nintedanib-plus-sildenafil group) or nintedanib at a dose of 150 mg twice daily plus placebo three times daily (nintedanib group) for 24 weeks. The primary end point was the change from baseline in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 12 (the total score ranges from 0 to 100, with higher scores indicating worse health-related quality of life). Secondary end points included measures of dyspnea and safety.ResultsA total of 274 patients underwent randomization. There was no significant difference in the adjusted mean change from baseline in the SGRQ total score at week 12 between the nintedanib-plus-sildenafil group and the nintedanib group (-1.28 points and -0.77 points, respectively; P=0.72). A benefit from sildenafil treatment was not observed with regard to dyspnea as measured with the use of the University of California, San Diego, Shortness of Breath Questionnaire. No new safety signals were observed, as compared with previous trials.ConclusionsIn patients with IPF and a DlCO of 35% or less of the predicted value, nintedanib plus sildenafil did not provide a significant benefit as compared with nintedanib alone. No new safety signals were identified with either treatment regimen in this population of patients. (Funded by Boehringer Ingelheim; INSTAGE ClinicalTrials.gov number, NCT02802345.)