Table 3.
Summary of trials related to recent emerging targeted therapies and initial combination therapies
| Name of trial | Treatment of investigation | Sample size, n | NYHA class | Primary endpoint | Result | Reference |
|---|---|---|---|---|---|---|
| Emerging therapies | ||||||
| SERAPHIN | Macitentan 3 or 10 mg qd (vs. placebo) | 742 (IPAH or CTD-PAH on background PAH therapy) | II/III | Death or disease progression | 3 mg dose (HR, 0.70; p = 0.01) | [37] |
| 10 mg dose: (HR, 0.55; p < 0.001) | ||||||
| PATENT-1 | Riociguat 2.5 mg tid (vs. placebo) | 396 (IPAH and others on background PAH therapy) | II/III | 6MWT at week 12 | Significant increase in 6MWT (30 m vs. –6 m, p < 0.001) | [38] |
| GRIPHON | Selexipag (maximal dose vs. placebo) | 1,156 (IPAH/HPAH or CHD-PAH on background PAH therapy) | II/III | Death or PAH complication | Significant benefit (27% vs. 41.6%; HR, 0.60; p < 0.001) | [39] |
| Combination therapy | ||||||
| Retrospective Study | Initial triple combination: IV epoprostenol, bosentan, and sildenafil | 19 (treatment-naïve newly diagnosed IPAH/HPAH or anorexigen-PAH patients) | III/IV | 6MWT, mPAP, CI, and PVR | Significant improvement of all 4 parameters at month 4 and beyond | [49] |
| AMBITION randomized control trial | Initial double combination: ambrisentan 10 mg qd + tadalafil 40 mg qd vs. monotherapy vs. placebo | 500 (treatment-naïve newly diagnosed PAH patients) | II/III | Primary endpoint: composite of death, PAH hospitalization, disease progression, or unsatisfactory clinical response | Significant benefit with initial combination therapy (combination:mono:placebo = 18%:34%:28%) | [40] |
| Prospective, multicenter, open-label trial | Initial double combination: ambrisentan 10 mg qd + tadalafil 40 mg qd for 36 weeks | 24 (treatment-naïve newly diagnosed SSc-PAH patients) | II/III | Co-primary endpoint: RV mass and PVR | Significant improvement of coprimary endpoints | [50] |
| Retrospective multi-center study | Initial combination therapy: bosentan, ambrisentan, sildenafil, tadalafil, and epoprostenol within < 90 days | 189 | II–IV | Hemodynamic status | Significant benefit with initial combination therapy compared with monotherapy | [51] |
NYHA, New York Heart Association; SERAPHIN, Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome; qd, once a day; IPAH, idiopathic pulmonary arterial hypertension; CTD-PAH, connective tissue disease-related pulmonary arterial hypertension; PAH, pulmonary arterial hypertension; HR, hazard ratio; PATENT-1, A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH); tid, three times a day; 6MWT, 6-minute walk test; GRIPHON, Selexipag (ACT-293987) in Pulmonary Arterial Hypertension; HPAH, heritable pulmonary arterial hypertension; IV, intravenous; mPAP, mean pulmonary arterial pressure; CI, cardiac index; PVR, pulmonary vascular resistance; AMBITION, A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH); SSc-PAH, scleroderma-associated pulmonary arterial hypertension; RV, right ventricle.