Characteristics of RCTs with PAH drugs interfering with the prostacyclin pathway (prostacyclin analogues and prostacyclin receptors agonists)
| Drug(s) tested | Study | Patients number | Duration (weeks) | Background Therapy | Primary end point | Main results |
|---|---|---|---|---|---|---|
| Epoprostenol | Barst68 | 116 | 52 | No | CW | CW not improved |
| Rubin72 | 23 | 12 | No | 6MWD | 6MWD improved Haemodynamics improved | |
| Barst13 | 81 | 12 | No | 6MWD | 6MWD improved Haemodynamics improvedSurvival improved | |
| Badesch73 | 111 | 12 | No | 6MWD | 6MWD improved | |
| Treprostinil | Subcutaneous—pivotal study74 | 470 | 12 | No | 6MWD | 6MWD improved Haemodynamics improved Pain at infusion site |
| Inhalative* TRIUMPH75 | 235 | 12 | Bosentan or sildenafil | 6MWD | 6MWD improvement (+20 m at peak, +12 m at trough) TTCW not improved | |
| Orally*—Freedom M76 | 185 | 16 | No | 6MWD | 6MWD improvement (+26 m at peak, +17 m at trough) TTCW not improved | |
| Orally*—Freedom C177 | 354 | 16 | ERA and/or PDE-5i | 6MWD | 6MWD not improved TTCW not improved | |
| Orally*—Freedom C278 | 310 | 16 | ERA and/or PDE-5i | 6MWD | 6MWD not improved TTC not improved | |
| Inhaled Iloprost | AIR79 | 203 | 12 | No | 6MWD and FC | 6MWD and WHO FC improved Haemodynamics improved at peak |
| STEP66 | 67 | 12 | Bosentan | 6MWD | 6MWD improved (p=0.05) TTCW improved | |
| COMBI80 | 40 | 12 | Bosentan | 6MWD (–) | Terminated for futility 6MWD not improved No clinical improvement | |
| Beraprost* | ALPHABET69 | 130 | 12 | No | 6MWD | 6MWD improved Haemodynamics not improved |
| Selexipag* | Phase 270 | 43 | 17 | ERA and/or PDE-5i | PVR | PVR improved 6MWD not improved |
| GRIPHON71 | 1156 | 74 | ERA and/or PDE-5i | TTCW | TTCW improved |
Modified from Galiè N et al.12
Note that most of the listed RCT data were derived from studies in adults with PAH. Healthcare providers must obtain valid information on the approval of any of the listed medications for use in paediatric PAH in the according country.
*This drug is not approved by the EMA at the time of submission of this manuscript.
6MWD, 6 min walk distance; CW, clinical worsening; EMA, European Medicines Agency; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase 5 inhibitor; RCT, randomised controlled trial; TTCW, time to clinical worsening.