Overview of clinical trials in pulmonary arterial hypertension (PAH) and chronic thromboembolic hypertension (CTEPH) in 2015
| First author [ref.] | Therapy | Diagnosis | Patients n | Study design | Follow-up | Primary end-point(s) | Conclusion |
| Chen [9] | Pulmonary artery denervation | WHO group 1, 2 and 4 | 66 | Phase II, non-randomised, open-label study | 1 year | Haemodynamic, functional and clinical response | PADN procedure was associated with favourable 1-year outcomes |
| Khan [10] | Ranolazine 1000 mg twice daily | PAH | 11 | Phase I | 3 months | Safety and tolerability | No major adverse events |
| Ruiter [11] | Intravenous iron | Iron-deficient iPAH | 15 | Open-label intervention study | 12 weeks | Change in 6MWD | No significant increase in 6MWD |
| Hassoun [12] | Tadalafil 40 mg and ambrisentan 10 mg | SSc-PAH | 24 | Open-label, prospective clinical trial | 36 weeks | Changes in PVR and RV mass | Significant decrease in PVR and RV mass |
| Galiè [13] | Tadalafil 40 mg and/or ambrisentan 10 mg | PAH NYHA II–III | 500 | Randomised, double-blind, phase 3–4 study | 24 weeks | First event of clinical failure | HR for event of clinical failure was significantly reduced in combination therapy group compared to mono therapy groups |
| Ehlken [14] | Low-dose exercise training 4–7 days per week | PAH, CTEPH | 87 | Randomised controlled trial | 15 weeks | Change in peak V′O2 per kg | Peak V′O2 per kg increased after low-dose exercise training |
| Frost [15] | Imatinib | PAH | 78 | Open-label extension study | Up to 204 weeks | Long-term safety and tolerability | SAEs and safety concerns preclude the use of imatinib in the treatment of PAH |
| Granton [16] | Endothelial NO synthase gene-enhanced progenitor cell therapy | PAH refractory to PAH therapy | 7 | Phase I, dose-escalating trial | 6 months | Tolerability | Delivery of endothelial progenitor cells overexpressing endothelial NO synthase was tolerated haemodynamically in patients with PAH |
| McLaughlin [17] | Addition of bosentan/placebo to sildenafil | PAH patients on sildenafil therapy | 334 | Double-blind, event-driven trial | Mean±sd 39.7±22.6 months | Time to morbidity/mortality event | No significant effect of addition of bosentan to sildenafil on time to morbidity/mortality was observed |
| Speich [18] | Imatinib | PAH | 15 | Open-label, observational study | Median 37 months | Efficacy and tolerability | Long-term treatment with imatinib may improve functional class and quality of life The occurrence of 5% SDH per patient-year is concerning |
| Provencher [19] | Thermostable epoprostenol sodium versus epoprostenol sodium | PAH | 16 | Multicentre, open-label, single-arm study | 4 weeks | HRQoL, ease of administration and change in dose from baseline | No significant improvement in HRQoL was measured Subjects preferred the thermostable product The products had similar safety and efficacy profiles |
| Galiè [20] | Riociguat and sildenafil | PAH patients on sildenafil therapy | 17 | Blinded, randomised controlled and extension study | 12 weeks, thereafter extension | Change in supine SBP and safety | No difference in SBP was observed Potentially unfavourable safety signals with sildenafil plus riociguat were observed |
| Rubin [21] | Riociguat | PAH | 396 | Open-label extension study | Mean 95 weeks | Safety, tolerability and efficacy (6MWD, WHO functional class) | Long-term riociguat was well tolerated in patients with PAH Data support sustained efficacy on 6MWD and WHO functional class |
| Simonneau [22] | Riociguat | CTEPH or persistent PH after PEA | 237 | Open label extension study | Mean 83 weeks | Safety, tolerability and efficacy (6MWD, WHO functional class) | Long-term riociguat was well tolerated in patients with CTEPH Data support sustained efficacy on 6MWD and WHO functional class |
| Chin [23] | Treprostinil sodium | PAH | 206 | Open-label extension study | Up to 24 months | 6MWD | Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months |
| Sitbon [24] | Selexipag versus placebo | PAH | 1156 | Blinded, randomised controlled trial | Median 63.7 weeks (placebo), 70.7 weeks (selexipag) | Time-to-event, composite of death or a complication related to PAH | The risk for the primary composite end-point was significantly lower among patients on selexipag compared to patients on placebo |
WHO: World Health Organisation; iPAH: idiopathic pulmonary arterial hypertension; SSc-PAH: systemic sclerosis-associated pulmonary arterial hypertension; NYHA: New York Heart Association functional class; PH: pulmonary hypertension; PEA: pulmonary endarterectomy; 6MWD: 6-min walk distance; PVR: pulmonary vascular resistance; RV: right ventricular; V′O2: oxygen uptake; HRQoL: health-related quality of life; SBP: systolic blood pressure; PADN: pulmonary artery denervation; HR: hazard ratio; SAE: serious adverse event; SDH: subdural haematoma.