Table 5

Characteristics of RCTs with PAH drugs interfering with the prostacyclin pathway (prostacyclin analogues and prostacyclin receptors agonists)

Drug(s) testedStudyPatients numberDuration (weeks)Background TherapyPrimary end pointMain results
EpoprostenolBarst6811652NoCWCW not improved
Rubin722312No6MWD6MWD improved
Haemodynamics improved
Barst138112No6MWD6MWD improved
Haemodynamics improvedSurvival improved
Badesch7311112No6MWD6MWD improved
47012No6MWD6MWD improved
Pain at infusion site
Inhalative* TRIUMPH7523512Bosentan or sildenafil6MWD6MWD improvement (+20 m at peak, +12 m at trough)
TTCW not improved
Orally*—Freedom M7618516No6MWD6MWD improvement (+26 m at peak, +17 m at trough)
TTCW not improved
Orally*—Freedom C17735416ERA and/or PDE-5i6MWD6MWD not improved
TTCW not improved
Orally*—Freedom C27831016ERA and/or PDE-5i6MWD6MWD not improved
TTC not improved
Inhaled IloprostAIR7920312No6MWD and FC6MWD and WHO FC improved
Haemodynamics improved at peak
 STEP666712Bosentan6MWD6MWD improved (p=0.05)
TTCW improved
COMBI804012Bosentan6MWD (–)Terminated for futility
6MWD not improved
No clinical improvement
Beraprost*ALPHABET6913012No6MWD6MWD improved
Haemodynamics not improved
Selexipag*Phase 2704317ERA and/or PDE-5iPVRPVR improved
6MWD not improved
GRIPHON71115674ERA and/or PDE-5iTTCWTTCW 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.