Table 1.
Patients, etiology, end points, treatment effects, and adverse reactions in the Pivotal Phase III Randomized Controlled Trials of the US Food and Drug Administration approved prostanoids for treatment of pulmonary arterial hypertension in adults.
| Rubin et al. [20] | Barst et al. [21] | Badesch et al. [22] | AIR [23] | Simmoneau et al. [24] | TRIUMPH-1 [25] | FREEDOM-M [26] | |
|---|---|---|---|---|---|---|---|
| Patients (no.) | 23 | 81 | 111 | 203 | 470 | 235 | 349 |
| Drug | EPOPROSTENOL | ILOPROST | TREPROSTINIL | ||||
| Dosing/route | 20–40 ng/Kg/min iv. | 2.5–5 μg inh. x6–9 | 20–80 ng/Kg/min sc. | 18–54 μg inh. x4 | 0.125–12 mg bid os | ||
| Follow-up (months) | 2 | 3 | 3 | 3 | 3 | 3 | 3 |
| Etiology (%)* | |||||||
| IPAH | 100 | 100 | — | 51 | 58 | 56 | 74 |
| CTD | — | — | 100 | 13 | 19 | 33 | 18 |
| CHD | — | — | — | — | 24 | — | 7 |
| CTEPH | — | — | — | 33 | — | — | — |
| Anorexigen use | — | — | — | 3 | — | — | — |
| HIV | — | — | — | — | — | — | 1 |
| Functional class (%) | |||||||
| NYHA/WHO II | 9 | — | 5 | — | 11 | — | 34 |
| NYHA/WHO III | 65 | 75 | 78 | 59 | 82 | 98 | 66 |
| NYHA/WHO IV | 26 | 25 | 17 | 41 | 7 | 2 | — |
| Primary end point | Hemodynamics | Hemodynamics | 6MWD | Combined† | 6MWD | 6MWD | 6MWD |
| Treatment effects | |||||||
| Δ6MWD (m) | 45 | 47 | 94 | 36 | 16 | 20 | 23 |
| Hemodynamics | Improved | Improved | Improved | Improved | Improved | N/A | N/A |
| Clinical worsening | Reduced | Reduced‡ | No change | Reduced | Reduced | No change | No change |
| Adverse reactions | Flushing, headache, vomiting, jaw pain, hypotension | Flushing, cough, headache, trismus | Infusion site pain, cough, headache | Pharyngeal pain/throat irritation, cough | Nausea, diarrhea, headache, jaw pain | ||
AIR: Aerosolized Iloprost Randomized; TRIUPMH: TReprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension; FREEDOM-M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension; iv.: intravenous; inh.: inhalation; sc.: subcutaneous; bid: twice daily; os: oral; *sum of percentage may not be 100% for rounding to the nearest unit; 0.5 is rounded to the upper unit; IPAH: idiopathic pulmonary arterial hypertension; CTD: connective tissue disease; CHD: congenital heart disease (congenital systemic-to-pulmonary shunts); CTEPH: chronic thromboembolic pulmonary hypertension; HIV: human immunodeficiency virus; NYHA: New York Heart Association; WHO: World Health Organization; 6MWD: 6 min walk distance; †combined epoprostenol end point of improvement in NYHA functional class and >10% in 6MWD; Δ: mean (or median) change from baseline;‡ significantsurvival benefit (P = 0.003) was observed in epoprostenol patients.