title: Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia.
abstract: BACKGROUND
  Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality.
  
  
  OBJECTIVE
  To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group.
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks.
  
  
  RESULTS
  Sixty patients (42 men; mean age, 66.6 ± 9.2 yr), with a mean pulmonary artery pressure of 36.0 (± 8.9) mm Hg, PVRi 13.0 (± 6.7) Wood Units/m(2) and reduced cardiac index of 2.21 (± 0.5) L/min/m(2) were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change in functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group).
  
  
  CONCLUSIONS
  This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP. Clinical trial registered with www.clinicaltrials.gov (NCT 00637065).
authors.affiliation: 1 Interstitial Lung Disease Unit.
authors.forename: Tamera J
authors.initials: TJ
authors.lastname: Corte
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Keir
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimopoulos
authors.forename: Luke
authors.initials: L
authors.lastname: Howard
authors.forename: Paul A
authors.initials: PA
authors.lastname: Corris
authors.forename: Lisa
authors.initials: L
authors.lastname: Parfitt
authors.forename: Claire
authors.initials: C
authors.lastname: Foley
authors.forename: Monica
authors.initials: M
authors.lastname: Yanez-Lopez
authors.forename: Daphne
authors.initials: D
authors.lastname: Babalis
authors.forename: Philip
authors.initials: P
authors.lastname: Marino
authors.forename: Toby M
authors.initials: TM
authors.lastname: Maher
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Renzoni
authors.forename: Lisa
authors.initials: L
authors.lastname: Spencer
authors.forename: Charlie A
authors.initials: CA
authors.lastname: Elliot
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Birring
authors.forename: Katherine
authors.initials: K
authors.lastname: O'Reilly
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gatzoulis
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wort
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D054988:Idiopathic Interstitial Pneumonias / Q000150:complications*; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan
keywords: clinical trial; hypertension; interstitial lung diseases; pulmonary