title: Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor.
  
  
  OBJECTIVE
  To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300).
  
  
  METHODS
  Academic and private hospitals.
  
  
  METHODS
  Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans.
  
  
  METHODS
  Ambrisentan, 10 mg/d, or placebo.
  
  
  METHODS
  Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function.
  
  
  RESULTS
  The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point.
  
  
  CONCLUSIONS
  The study was terminated early.
  
  
  CONCLUSIONS
  Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations.
  
  
  BACKGROUND
  Gilead Sciences.
authors: Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, 1959 NE Pacific, Campus Box 356175, Seattle, WA 98195, USA.
authors: Ganesh
authors: G
authors: Raghu
authors: Juergen
authors: J
authors: Behr
authors: Kevin K
authors: KK
authors: Brown
authors: Jim J
authors: JJ
authors: Egan
authors: Steven M
authors: SM
authors: Kawut
authors: Kevin R
authors: KR
authors: Flaherty
authors: Fernando J
authors: FJ
authors: Martinez
authors: Steven D
authors: SD
authors: Nathan
authors: Athol U
authors: AU
authors: Wells
authors: Harold R
authors: HR
authors: Collard
authors: Ulrich
authors: U
authors: Costabel
authors: Luca
authors: L
authors: Richeldi
authors: Joao
authors: J
authors: de Andrade
authors: Nasreen
authors: N
authors: Khalil
authors: Lake D
authors: LD
authors: Morrison
authors: David J
authors: DJ
authors: Lederer
authors: Lixin
authors: L
authors: Shao
authors: Xiaoming
authors: X
authors: Li
authors: Patty S
authors: PS
authors: Pedersen
authors: A Bruce
authors: AB
authors: Montgomery
authors: Jason W
authors: JW
authors: Chien
authors: Thomas G
authors: TG
authors: O'Riordan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan