Randomised controlled trials (RCTs) of pulmonary vasodilators in pulmonary hypertension (PH)-associated interstitial lung diseases (ILDs)
First author [reference] | Year | Name of RCT | Study population | Drug | Duration | Primary end-point | Primary end-point reached |
King [76] | 2008 | BUILD-1 | IPF | Bosentan | 12 months | Change in 6MWD | N |
Seibold [77] | 2010 | BUILD-2 | SSc | Bosentan | 12 months | Change in 6MWD | N |
Zisman [78] | 2010 | STEP-IPF | IPF | Sildenafil | 12 weeks | Change in 6MWD | N |
King [79] | 2011 | BUILD-3 | IPF | Bosentan | 57 months | Combined# | N |
Raghu [80] | 2013 | MUSIC | IPF | Macitentan | 12 months | Change in FVC | N |
Raghu [81] | 2013 | ARTEMIS-IPF | IPF | Ambrisentan | 12 months | Combined¶,+ | N |
Corte [82] | 2014 | IPF/NSIP | Bosentan | 16 weeks | Change in PVRI | N | |
Kolb [83] | 2018 | INSTAGE | IPF | Sildenafil | 12 weeks | Change in SGRQ | N |
Nathan [84] | 2019 | RISE-IIP | IIP | Riociguat | 12 months | Change in 6MWD+ | N |
Nathan [85] | 2020 | PF-ILD | Inhaled NO | 8 weeks | Change in MVPA§ | Y | |
Behr [86] | 2021 | SP-IPF | IPF | Sildenafil | 12 months | Combinedƒ | N |
Waxman [87] | 2021 | INCREASE | IIP | Inhaled treprostinil | 16 weeks | Change in 6MWD | Y |
IPF: idiopathic pulmonary fibrosis; 6MWD: 6-min walk distance; N: no; SSc: systemic sclerosis; FVC: forced vital capacity; NSIP: nonspecific idiopathic pneumonia; PVRI: pulmonary vascular resistance index; SGRQ: St George's Respiratory Questionnaire; IIP: idiopathic interstitial pneumonia; PF: pulmonary fibrosis; NO: nitric oxide; Y: yes; MVPA: moderate/vigorous physical activity. #: a decrease of FVC from baseline in FVC ≥10% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥15% or acute exacerbation of idiopathic pulmonary fibrosis or death. ¶: the first occurrence of either a decrease of ≥10% in FVC and a decrease of ≥5% in DLCO or a decrease of ≥5% in FVC and a decrease of ≥15% in DLCO; respiratory hospitalisation (hospitalisation involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxaemia or radiographic findings on chest radiograph or high-resolution computed tomography scan; all-cause mortality. +: study terminated early because of increased severe side-effects and mortality in the treated arm. §: MVPA measured via actigraphy through a wrist-worn medical-grade physical activity monitoring device. ƒ: disease progression, defined as either a relevant decline in 6MWD, respiratory-related admission to hospital or all-cause mortality.