Trial [ref.] | Background therapy/study drug | Design | Patients | Subjects n | Duration weeks | Primary end-point | Efficacy | |
Primary end-point | TTCW | |||||||
BREATHE-2 [30] | Epoprostenol/bosentan | Upfront RCT | IPAH, SSc, SLE | 33 | 16 | TPR | - | ND |
STEP [31] | Bosentan/iloprost (inhaled) | Sequential RCT | PAH | 67 | 12 | 6MWD | - | + |
COMBI [32] | Bosentan/iloprost (inhaled) | Sequential open label | IPAH | 40 | 12 | 6MWD | - | - |
PACES [33] | Epoprostenol/sildenafil | Sequential RCT | IPAH, CTD, CHD | 277 | 12 | 6MWD | + | + |
TRIUMPH-1 [34] | Sildenafil, bosentan or both/treprostinil (inhaled) | Sequential RCT | PAH | 235 | 12 | 6MWD | + | - |
FREEDOM-C [35] | Sildenafil, ERA or both/treprostinil (oral) | Sequential RCT | PAH | 354 | 16 | 6MWD | - | - |
IMPRES [36] | ≥2 PAH-specific therapies/imatinib | Sequential RCT | IPAH, HPAH, CTD, CHD | 202 | 24 | 6MWD | + | - |
PHIRST [37] | Bosentan/tadalafil | Sequential RCT | PAH | 216# | 16 | 6MWD | - | ND |
EARLY [23] | Sildenafil/bosentan | Sequential RCT | PAH | 28¶ | 24 | PVR | + | ND |
TTCW: time to clinical worsening; ERA: endothelin receptor antagonist; RCT: randomised controlled trial; IPAH: idiopathic PAH; SSc: systemic sclerosis; SLE: systemic lupus erythematosis; CTD: connective tissue disease; CHD: congenital heart disease; HPAH: heritable PAH; TPR: total pulmonary resistance; 6MWD: 6-min walk distance; PVR: pulmonary vascular resistance; ND: not determined; +: met end-point; -: did not meet end-point. #: only patients included in the subgroup analysis of patients who were receiving concomitant bosentan at baseline were included; ¶: only patients included in the subgroup analysis of patients who were receiving concomitant sildenafil at baseline were included.