Table 2.

Clinical trials evaluating oral prostanoid and nonprostanoid IP receptor agonists in the treatment of PAH

Trial	Study drug	n	Weeks	Background PAH therapy	Primary endpoint: treatment effect	Secondary endpoints
ALPHABET12	Beraprost	130	12	None	6MWD: 25 meters, P=0.04	Improvement in Borg dyspnea index versus placebo; no significant difference in functional class, hemodynamics or disease progression
Beraprost study group13	Beraprost	116	52	None	Disease progression: placebo 17% versus beraprost 29%, P=0.254	No significant difference in 12-month peak VO2, 6MWD, Borg dyspnea index, WHO functional class or hemodynamics
FREEDOM-C15	Treprostinil	350	16	100%	6MWD: 11 meters, P=0.07	Improvement in dyspnea fatigue index score; no significant difference in clinical worsening, functional class, Borg dyspnea score
FREEDOM-C216	Treprostinil	310	16	100%	6MWD: 10 meters, P=0.09	No significant difference in clinical worsening, Borg dyspnea score, NT-proBNP, functional class, CAMPHOR
FREEDOM-M17	Treprostinil	349	12	None	6 MWD: 26 meters, P=0.01	No significant difference in Borg dyspnea score, functional class or symptoms of PAH
Selexipag phase 2 study28	Selexipag	43	17	100%	ΔPVR: −30%, P<0.01	Improvement in cardiac index; no significant difference in Borg dyspnea score, NT-proBNP, 6MWD
GRIPHON29	Selexipag	1,156	64–71	80%	Disease progression: HR 0.6, P<0.001	Improvement in 6MWD (12 meters, P<0.01) and NT-proBNP, no significant difference in proportion with worsening functional class

Abbreviations: CAMPHOR, Cambridge Pulmonary Hypertension Outcome Review; HR, hazard ratio; IP, prostacyclin; MWD, minute walk distance; NT-proBNP, N-terminal probrain natriuretic peptide; PVR, pulmonary vascular resistance; PAH, pulmonary arterial hypertension; VO2, peak oxygen consumption; WHO, World Health Organization.