Characteristics of RCTs with PAH drugs interfering with the nitric oxide pathway (soluble guanylate cyclase stimulators, phosphodiesterase type-5 inhibitors)
| Drug(s) tested | Study | Patients number | Duration (weeks) | Background Therapy | Primary end point | Main results |
|---|---|---|---|---|---|---|
| Riociguat | PATENT45 | 443 | 12 | No or bosentan or prostanoids | 6MWD | 6MWD improved Haemodynamics improved |
| PATENT plus47 | 30 | 18 | Sildenafil | Supine SBP | Terminated for excess of SAE in the treated group | |
| Sildenafil | SUPER-148 | 277 | 12 | No | 6MWD | 6MWD improved TTCW not improved |
| Sastry49 | 22 | 12 | No | TT | TT improved | |
| Singh50 | 20 | 6 | No | 6MWD | 6MWD improved | |
| PACES51 | 264 | 16 | Epoprostenol | 6MWD | 6MWD improved TTCW and haemodynamics improved | |
| Iversen52 | 20 | 12 | bosentan | 6MWD | 6MWD not improved | |
| Pfizer study A1481243 | 103 | 12 | bosentan | 6MWD | 6MWD not improved | |
| Sildenafil (paediatric) | STARTS-139 | 235 | 16 | No | TT | %change in VO2 max, functional class and hemodynamic improved with medium and high doses |
| STARTS-240 | 206 | 208 | No | Survival | Survival improved | |
| Tadalafil | PHIRST53 | 405 | 16 | No or bosentan (54%) | 6MWD | 6MWD improved (in bosentan treated patients +23 m, 95% CI –2 to 48 m) TTCW improved |
| Vardenafil* | EVALUATION54 | 66 | 12 | No | 6MWD | 6MWD improved 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 for use in adult PAH at the time of submission of this manuscript.
6MWD, 6 min walk distance; EMA, European Medicines Agency; PAH, pulmonary arterial hypertension; RCT, randomised controlled trial; TTCW, time to clinical worsening; TT, treadmill test.