title: BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Department of Medicine, University of California San Francisco, 505 Parnassus Avenue, Box 0120, San Francisco, CA 94143-0120, USA. tking@medicine.ucsf.edu
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.forename: Fernando
authors.initials: F
authors.lastname: Martinez
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leconte
authors.forename: Adele
authors.initials: A
authors.lastname: Morganti
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roux
authors.forename: Juergen
authors.initials: J
authors.lastname: Behr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D018450:Disease Progression; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D011788:Quality of Life; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D014797:Vital Capacity
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan