RATIONALE: A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed. OBJECTIVES: To demonstrate that bosentan delays IPF worsening or death. METHODS: Prospective, randomized (2:1), double-blind, placebo-controlled, event-driven, parallel-group, morbidity-mortality trial of bosentan in adults with IPF of less than 3 years' duration, confirmed by surgical lung biopsy, and without extensive honeycombing on high-resolution computed tomography. The primary endpoint was time to IPF worsening (a confirmed decrease from baseline in FVC ≥ 10% and diffusing capacity of the lung for carbon monoxide ≥ 15%, or acute exacerbation of IPF) or death up to End of Study. Effects of bosentan on health-related quality of life, dyspnea, and the safety and tolerability of bosentan were investigated. MEASUREMENTS AND MAIN RESULTS:Six hundred sixteen patients were randomized to bosentan (n=407) orplacebo (=209). No significant difference between treatment groups was observed in the primary endpoint analysis (hazard ratio, 0.85; 95% confidence interval, 0.66-1.10; P=0.2110). No treatment effects were observed on health-related quality of life or dyspnea. Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide. The safety profile for bosentan was similar to that observed in other trials. CONCLUSIONS: The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met. Bosentan was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00391443).
RCT Entities:
RATIONALE: A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed. OBJECTIVES: To demonstrate that bosentan delays IPF worsening or death. METHODS: Prospective, randomized (2:1), double-blind, placebo-controlled, event-driven, parallel-group, morbidity-mortality trial of bosentan in adults with IPF of less than 3 years' duration, confirmed by surgical lung biopsy, and without extensive honeycombing on high-resolution computed tomography. The primary endpoint was time to IPF worsening (a confirmed decrease from baseline in FVC ≥ 10% and diffusing capacity of the lung for carbon monoxide ≥ 15%, or acute exacerbation of IPF) or death up to End of Study. Effects of bosentan on health-related quality of life, dyspnea, and the safety and tolerability of bosentan were investigated. MEASUREMENTS AND MAIN RESULTS: Six hundred sixteen patients were randomized to bosentan (n=407) or placebo (=209). No significant difference between treatment groups was observed in the primary endpoint analysis (hazard ratio, 0.85; 95% confidence interval, 0.66-1.10; P=0.2110). No treatment effects were observed on health-related quality of life or dyspnea. Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide. The safety profile for bosentan was similar to that observed in other trials. CONCLUSIONS: The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met. Bosentan was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00391443).
Authors: Yael Aschner; Anthony P Khalifah; Natalie Briones; Cory Yamashita; Lior Dolgonos; Scott K Young; Megan N Campbell; David W H Riches; Elizabeth F Redente; William J Janssen; Peter M Henson; Jan Sap; Nathalie Vacaresse; Andras Kapus; Christopher A G McCulloch; Rachel L Zemans; Gregory P Downey Journal: Am J Pathol Date: 2014-03-17 Impact factor: 4.307
Authors: Aline C Oliveira; Chunhua Fu; Yuanqing Lu; Mason A Williams; Liya Pi; Mark L Brantly; Corey E Ventetuolo; Mohan K Raizada; Borna Mehrad; Edward W Scott; Andrew J Bryant Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-07-31 Impact factor: 5.464
Authors: Belinda N Rivera-Lebron; Paul R Forfia; Maryl Kreider; James C Lee; John H Holmes; Steven M Kawut Journal: Chest Date: 2013-08 Impact factor: 9.410