BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease lacking effective treatment.


OBJECTIVE
To determine the effects of bosentan on exercise capacity and time to disease progression in patients with IPF.


METHODS
In a double-blind, multicenter trial, patients with IPF were randomized to receive oral bosentan 62.5 mg twice daily for 4 weeks, increased to 125 mg twice daily thereafter, or placebo, for 12 months or longer. The primary efficacy endpoint was change from baseline up to Month 12 in exercise capacity, as measured by a modified six-minute-walk test. Secondary endpoints were time to death or disease progression (worsening pulmonary function tests [PFTs] or acute decompensation), change in PFT scores, and quality of life (QOL) assessed using Short-Form 36 and St. George's Respiratory Questionnaire.


RESULTS
A total of 158 patients randomly received bosentan (n = 74) or placebo (n = 84). Bosentan showed no superiority over placebo in six-minute-walk distance (6MWD) up to Month 12, the primary efficacy endpoint. A trend in favor of bosentan was observed in the secondary endpoint of time to death or disease progression (hazard ratio [HR], 0.613; 95% confidence interval [CI], 0.328-1.144; P = 0.119), which was more pronounced in a patient subgroup diagnosed using surgical lung biopsy (post hoc analysis; HR, 0.315; 95% CI, 0.126-0.789; P = 0.009). Changes from baseline up to Month 12 in assessments of dyspnea and QOL favored treatment with bosentan. No unexpected adverse events were reported.


CONCLUSIONS
Bosentan treatment in patients with IPF did not show superiority over placebo on 6MWD. A trend in delayed time to death or disease progression, and improvement in QOL, was observed with bosentan. The more pronounced treatment effect in patients with biopsy-proven IPF warrants further investigation. Clinical trial registered with www.clinicaltrials.gov (NCT 00071461).
King
Talmadge E
TE
Department of Medicine, UCSF, 505 Parnassus Avenue, Room M994, San Francisco, CA 94110, USA. tking@medicine.ucsf.edu
Behr
Jürgen
J
Brown
Kevin K
KK
du Bois
Roland M
RM
Lancaster
Lisa
L
de Andrade
Joao A
JA
Stähler
Gerd
G
Leconte
Isabelle
I
Roux
Sébastien
S
Raghu
Ganesh
G
D000284:Administration, Oral; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D036542:Tomography, Spiral Computed; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan