Randomised controlled trials (RCTs) of pulmonary vasodilators in pulmonary hypertension (PH)-associated interstitial lung diseases (ILDs)

First author [reference]YearName of RCTStudy populationDrugDurationPrimary end-pointPrimary end-point reached
King [76]2008BUILD-1IPFBosentan12 monthsChange in 6MWDN
Seibold [77]2010BUILD-2SScBosentan12 monthsChange in 6MWDN
Zisman [78]2010STEP-IPFIPFSildenafil12 weeksChange in 6MWDN
King [79]2011BUILD-3IPFBosentan57 monthsCombined#N
Raghu [80]2013MUSICIPFMacitentan12 monthsChange in FVCN
Raghu [81]2013ARTEMIS-IPFIPFAmbrisentan12 monthsCombined¶,+N
Corte [82]2014IPF/NSIPBosentan16 weeksChange in PVRIN
Kolb [83]2018INSTAGEIPFSildenafil12 weeksChange in SGRQN
Nathan [84]2019RISE-IIPIIPRiociguat12 monthsChange in 6MWD+N
Nathan [85]2020PF-ILDInhaled NO8 weeksChange in MVPA§Y
Behr [86]2021SP-IPFIPFSildenafil12 monthsCombinedƒN
Waxman [87]2021INCREASEIIPInhaled treprostinil16 weeksChange in 6MWDY

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.