Table 2.

Major trials for prostanoids.

Authors	Study	Study Size	Duration	Primary Endpoint	Secondary Endpoints
Epoprostenol
Barst et al. [1996]	A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) with Conventional Therapy for Primary Pulmonary Hypertension	81	12 weeks	6MWD	QoL, hemodynamics, survival
Badesch et al. [2000]	Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial	111	12 weeks	6MWD	Hemodynamic, signs and symptoms of PH and scleroderma, survival
Treprostinil
Simonneau et al. [2002]	Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial	470	12 weeks	6MWD	Principal efficacy endpoints: Signs and symptoms of PH, Dyspnea Fatigue Rating, Number of deaths, lung transplantations or discontinuations for clinical deterioration. Borg Dyspnea Scale, Hemodynamics, Minnesota Living with Heart Failure Questionnaire
Tapson et al. [2006]	Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial	16	12 weeks	6MWD	Naughton–Balke treadmill time, Borg dyspnea score, hemodynamics
McLaughlin et al. [2010]	Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial	235	12 weeks	6MWD	Time to clinical worsening, Borg Dyspnea Score, NYHA functional class, 12-week trough 6MWD, 6-week peak 6MWD, quality of life, PAH signs and symptoms
Tapson et al. [2012]	Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial	350	16 weeks	6MWD	Time to clinical worsening, clinical deterioration, combined ranking of 6MWD and Borg dyspnea score, Dyspnea fatigue index score
Tapson et al. [2013]	Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial	310	16 weeks	6MWD	Clinical worsening, Borg dyspnea score, combined walk distance and Borg score, NT-proBNP, WHO functional classification, the Cambridge Pulmonary Hypertension Outcome Review, signs and symptoms of PAH, and safety
Jing et al. [2013]	Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial	349	12 weeks	6MWD	Trough 6MWD, Time to clinical worsening, combined 6MWD and Borg, WHO functional class, Dyspnea-fatigue index, symptoms of PAH, 6MWD at week 4 and 8
Iloprost
Olschewski et al. [2002]	Inhaled iloprost for severe pulmonary hypertension	203	12 weeks	increase in 6MWD by at least 10% and improvement in NYHA functional class	6MWD, NYHA class, Mahler Dyspnea Index scores, hemodynamic variables, QoL, clinical deterioration, death, need for transplantation
Hoeper et al. [2000]	Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue	24	12 months		6MWD, hemodynamics
Selexipag
Simonneau et al. [2012]	Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension	43	17 weeks	PVR	Additional hemodynamics, 6MWD, aggravation of PAH, Borg dyspnea score, WHO functional class, NT-proBNP
Sitbon et al. [2015]	Selexipag for the Treatment of Pulmonary Arterial Hypertension	1156	36 months	Composite of death or complication related to PAH	6MWD, WHO functional class, death or hospitalization

6MWD, 6-minute walk distance; IV, intravenous; NYHA, New York Heart Association; NT-proBNP, N-terminal pro-brain natriuretic peptide; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; QoL, quality of life; WHO, World Health Organization.