BUILD-3: A Randomized, Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis

Abstract

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).

Interstitial Lung Disease in Systemic Sclerosis: Diagnosis and Management

“…Secondary end points of time to death and worsening of PFTs were also no different [55]. This negative study mirrors negative results seen in trials of endothelin receptor antagonists in IPF [56].…”

Staging of idiopathic pulmonary fibrosis: past, present and future

“…Reproduced with modification from [21] with permission from the publisher. [14][15][16][17][18][19][20]. This approach to staging provides physicians with a general framework to monitor disease progression and advise patients.…”

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

“…The IFIGENIA trial was a multicentre, double-blind, randomised, placebo-controlled phase III trial which evaluated the effect of a high dose of oral NAC (i.e. 600 mg three times daily) together with low dose of Pirfenidone Antifibrotic CAPACITY 1 [23] Pirfenidone Antifibrotic CAPACITY 2 [23] Pirfenidone Antifibrotic ACE-IPF [24] Warfarin Anticoagulant TOMORROW [25] BIBF 1120 Tyrosine-kinase inhibitor DANIELS [26] Imatinib mesylate Tyrosine-kinase inhibitor STEP-IPF [27] Sildenafil Phosphodiesterase-5 inhibitor BUILD-1 [28] Bosentan Endothelin-receptor antagonist BUILD-3 [29] Bosentan Endothelin-receptor antagonist ARTEMIS-IPF [30] Ambrisentan Endothelin-receptor antagonist MUSIC-IPF [31] Macitentan Endothelin-receptor antagonist RAGHU [32] IFN-c Immunomodulation INSPIRE [33] IFN-c prednisone and azathioprine compared with prednisone and azathioprine alone [20]. The primary endpoint was the change in vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLCO) at 12 months.…”

“…Bosentan, an endothelin-1 receptor antagonist effective in pulmonary arterial hypertension, was initially tested in small trials for IPF because of its antifibrotic properties and showed some encouraging results, which were later replaced by disappointing results from larger trials [28,29]. In BUILD-1, a randomised, placebo-controlled, phase II trial, the primary end-point of change in 6MWD was not met.…”

“…However, a trend towards a delayed time to disease progression in favour of bosentan was observed and has been shown to be statistically significant in cases of ''atypical'' IPF appearance in high resolution computed tomography and hence diagnosed by surgical lung biopsy [28]. Subsequently, a larger double-blind, randomised, placebo-controlled trial (BUILD-3) explored the effect of bosentan on the time to IPF worsening or death, and no significant effects were observed when compared with placebo [29].…”