Bosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia (BPHIT)
Corte TJ1, Keir GJ, Dimopoulos K, Howard L, Corris PA, Parfitt L, Foley C, Yanez-Lopez M, Babalis D, Marino P, Maher TM, Renzoni EA, Spencer L, Elliot CA,Birring S, O'Reilly K, Gatzoulis MA, Wells AU, Wort SJ; for the BPHIT Study Group.
Am J Respir Crit Care Med. 2014 Jun 17.
Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP) confers important additional morbidity and mortality. Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist (ERA) 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 end point was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks. Main Results: Sixty patients (42 men; mean age 66.6±9.2 years), with a mean pulmonary artery pressure of 36.0 (±8.9) mmHg, PVRi 13.0 (±6.7) Wood Units.m2 and reduced cardiac index of 2.21 (±0.5) L/min/m2 were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter (RHC) 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 ≥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 haemodynamics, functional capacity or symptoms between the bosentan and placebo groups over 16 weeks. Our data does not support therefore the use of the dual ERA, bosentan in patients with PH and fibrotic IIP. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00637065.
KEYWORDS: Clinical Trial; Hypertension, Pulmonary; Lung Diseases, Interstitial