TABLE 3.
Clinical trials with drugs targeting inflammation in pulmonary arterial hypertension (PAH)
| Drug tested | ClinicalTrials.gov identifier | Study design | Study duration | Main inclusion criteria | Primary outcome measures | Secondary outcome measures |
| Modulation of cytokines pathway: anakinra and tocilizumab | ||||||
| Anakinra | NCT01479010 | Single-centre open-label pilot study: phase 1 and 2 | 4 weeks | PAH (excluding PAH-CTD, ILD, POPH) in FC III despite optimal PAH therapy | Change in peak V′O2 and in V′E/V′CO2 slope (CPET) | Change in biomarkers; correlation between changes in biomarkers and CPET measures |
| Anakinra | NCT03057028 | Single-centre open-label pilot study: phase 1 | 14 days | PAH (excluding PAH-CTD) in FC II or III despite optimal PAH therapy | Change 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 |
| Tocilizumab | NCT02676947 | Open-label: phase 2 (TRANSFORM-UK) | 24 weeks | PAH (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 | ||||||
| Ubenimex | NCT02736149 | Multicentre 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 study | Safety (adverse events) | Change in PVR, 6MWD, WHO FC and BNP/NT-proBNP |
| Ubenimex | NCT02664558 | Multicentre double-blind RCT versus placebo: phase 2 (LIBERTY) | 24 weeks | PAH on ≥1 PAH-specific therapies in WHO FC II or III | Change in PVR | Change 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.