First author [ref.] | Year (trial acronym) | Background therapy | Drug | Patients n | Duration | Primary end-point | Primary end-point met? |
Epoprostenol# | |||||||
Rubin [37] | 1990 | None | i.v. epoprostenol | 24 | 8 weeks | Change in total pulmonary resistance | Yes |
Barst [38] | 1996 | None | i.v. epoprostenol | 81 | 12 weeks | Change in 6MWD | Yes |
Badesch [39] | 2000 | None | i.v. epoprostenol | 111 | 12 weeks | Change in 6MWD | Yes |
Badesch[40] | 2009 | None | i.v. epoprostenol | 102 | 3 years | Survival | No |
Humbert[41] | 2004 (BREATHE-2) | None | i.v. epoprostenol with bosentan or placebo | 33 | 16 weeks | Change in total pulmonary resistance | No |
Simonneau [42] | 2008 (PACES) | i.v. epoprostenol | Sildenafil or placebo | 267 | 16 weeks | Change in 6MWD | Yes |
Iloprost¶ | |||||||
Olschewski [43] | 2002 | None | Inhaled iloprost or placebo | 203 | 12 weeks | Composite ≥10% increase in 6MWD and improvement in WHO FC | Yes |
Hoeper [44] | 2006 (COMBI) | Bosentan | Inhaled iloprost | 40 | 12 weeks | Change in 6MWD | No |
McLaughlin [45] | 2006 | Bosentan | Inhaled iloprost | 67 | 12 weeks | Change in 6MWD and WHO FC | Yes |
Treprostinil+ | |||||||
Simonneau [46] | 2002 | None | s.c. treprostinil or placebo | 470 | 12 weeks | Change in 6MWD | Yes |
Jing [47] | 2013 (FREEDOM-M) | None | Oral treprostinil or placebo | 349 | 12 weeks | Change in 6MWD | Yes |
Tapson [48] | 2012 (FREEDOM-C) | ERA, PDE-5i or both | Oral treprostinil or placebo | 350 | 16 weeks | Change in 6MWD | No |
Tapson [49] | 2013 (FREEDOM-C2) | ERA, PDE-5i or both | Oral treprostinil or placebo | 310 | 16 weeks | Change in 6MWD | No |
McLaughlin [50] | 2010 (TRIUMPH-I) | Bosentan or sildenafil | Inhaled treprostinil or placebo | 235 | 12 weeks | Change in 6MWD 10–60 min after inhalation | Yes |
Beraprost§ | |||||||
GaliÉ [51] | 2002 (ALPHABET) | None | Oral beraprost or placebo | 130 | 12 weeks | Change in 6MWD | Yes |
Barst [52] | 2003 | None | Oral beraprost or placebo | 116 | 12 months | Difference in disease progression | Yes |
Selexipag | |||||||
McLaughlin [53] | 2015 (GRIPHON) | None, ERA, PDE-5i or both | Oral selexipagƒ | 1156 | 3 years | Time to first morbidity or mortality event | Yes |
6MWD: 6-min walking distance; WHO: World Health Organization; FC: functional class; ERA: endothelin receptor agonist; PDE-5i: phosphodiesterase type 5 inhibitor. #: approved for continuous i.v. administration for pulmonary arterial hypertension (PAH) WHO FC III–IV by the US Food and Drug Administration (FDA) in 1995; ¶: approved for aerosol administration for PAH WHO FC III in the European Union and Australia in 2003, and PAH WHO FC III–IV by the FDA in 2004; +: approved for s.c. administration for PAH WHO FC II–IV by the FDA and Health Canada in 2002; §: approved for oral administration for idiopathic PAH in Japan in 1995 [36]; ƒ: not approved at time of publication.