• Tamera J Corte, Gregory J Keir, Konstantinos Dimopoulos, Luke Howard, Paul A Corris, Lisa Parfitt, Claire Foley, Monica Yanez-Lopez, Daphne Babalis, Philip Marino, Toby M Maher, Elizabeth A Renzoni, Lisa Spencer, Charlie A Elliot, Surinder S Birring, Katherine O'Reilly, Michael A Gatzoulis, Athol U Wells, Stephen J Wort, and BPHIT Study Group.
• 1 Interstitial Lung Disease Unit.
• Am. J. Respir. Crit. Care Med. 2014 Jul 15; 190 (2): 208-17.

RationalePulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality.ObjectivesTo evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group.MethodsIn 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.Measurements And Main ResultsSixty 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).ConclusionsThis 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).

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