TABLE 3

Clinical trials with drugs targeting inflammation in pulmonary arterial hypertension (PAH)

Drug testedClinicalTrials.gov identifierStudy designStudy durationMain inclusion criteriaPrimary outcome measuresSecondary outcome measures
Modulation of cytokines pathway: anakinra and tocilizumab
 AnakinraNCT01479010Single-centre open-label pilot study: phase 1 and 24 weeksPAH (excluding PAH-CTD, ILD, POPH) in FC III despite optimal PAH therapyChange in peak V′O2 and in V′E/V′CO2 slope (CPET)Change in biomarkers; correlation between changes in biomarkers and CPET measures
 AnakinraNCT03057028Single-centre open-label pilot study: phase 114 daysPAH (excluding PAH-CTD) in FC II or III despite optimal PAH therapyChange in peak V′O2 and ventilatory efficiency (CPET)Change in hs-CRP, NT-proBNP, IL-6 and symptoms of heart failure (MLHFQ); correlation between biomarkers and measures of exercise capacity
 TocilizumabNCT02676947Open-label: phase 2 (TRANSFORM-UK)24 weeksPAH (excluding PAH-CTD due to SLE, RA and MCTD)Safety (incidence and severity of adverse events); change in PVR (RHC)Change in 6MWD, NT-proBNP, WHO FC and QoL
Inflammation: ubenimex
 UbenimexNCT02736149Multicentre open-label extension study: phase 2 (LIBERTY-2)Variable (average 1 year)PAH on ≥1 PAH-specific therapies, in FC II or III, who completed the phase 2 studySafety (adverse events)Change in PVR, 6MWD, WHO FC and BNP/NT-proBNP
 UbenimexNCT02664558Multicentre double-blind RCT versus placebo: phase 2 (LIBERTY)24 weeksPAH on ≥1 PAH-specific therapies in WHO FC II or IIIChange in PVRChange in 6MWD, WHO FC, TTCW, QoL and NT-proBNP

CTD: connective tissue disease; ILD: interstitial lung disease; POPH: portopulmonary hypertension; FC: functional class; V′O2: oxygen uptake; V′E/V′CO2: ventilatory response (minute ventilation/carbon dioxide production); CPET: cardiopulmonary exercise testing; hs-CRP: high-sensitivity C-reactive protein; NT-proBNP: N-terminal pro-brain natriuretic peptide; IL-6: interleukin-6; MLHFQ: Minnesota Living with Heart Failure Questionnaire; SLE: systemic lupus erythematosus; RA: rheumatoid arthritis; MCTD: mixed connective tissue disease; PVR: pulmonary vascular resistance; RHC: right heart catheterisation; 6MWD: 6-min walk distance; WHO: World Health Organization; QoL: quality of life; RCT: randomised controlled trial; TTCW: time to clinical worsening.