Overview of clinical trials in pulmonary arterial hypertension (PAH) and chronic thromboembolic hypertension (CTEPH) in 2015

First author [ref.]TherapyDiagnosisPatients nStudy designFollow-upPrimary end-point(s)Conclusion
Chen [9]Pulmonary artery denervationWHO group 1, 2 and 466Phase II, non-randomised, open-label study1 yearHaemodynamic, functional and clinical responsePADN procedure was associated with favourable 1-year outcomes
Khan [10]Ranolazine 1000 mg twice dailyPAH11Phase I3 monthsSafety and tolerabilityNo major adverse events
Ruiter [11]Intravenous ironIron-deficient iPAH15Open-label intervention study12 weeksChange in 6MWDNo significant increase in 6MWD
Hassoun [12]Tadalafil 40 mg and ambrisentan 10 mgSSc-PAH24Open-label, prospective clinical trial36 weeksChanges in PVR and RV massSignificant decrease in PVR and RV mass
Galiè [13]Tadalafil 40 mg and/or ambrisentan 10 mgPAH NYHA II–III500Randomised, double-blind, phase 3–4 study24 weeksFirst event of clinical failureHR 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 weekPAH, CTEPH87Randomised controlled trial15 weeksChange in peak VO2 per kgPeak VO2 per kg increased after low-dose exercise training
Frost [15]ImatinibPAH78Open-label extension studyUp to 204 weeksLong-term safety and tolerabilitySAEs and safety concerns preclude the use of imatinib in the treatment of PAH
Granton [16]Endothelial NO synthase gene-enhanced progenitor cell therapyPAH refractory to PAH therapy7Phase I, dose-escalating trial6 monthsTolerabilityDelivery of endothelial progenitor cells overexpressing endothelial NO synthase was tolerated haemodynamically in patients with PAH
McLaughlin [17]Addition of bosentan/placebo to sildenafilPAH patients on sildenafil therapy334Double-blind, event-driven trialMean±sd 39.7±22.6 monthsTime to morbidity/mortality eventNo significant effect of addition of bosentan to sildenafil on time to morbidity/mortality was observed
Speich [18]ImatinibPAH15Open-label, observational studyMedian 37 monthsEfficacy and tolerabilityLong-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 sodiumPAH16Multicentre, open-label, single-arm study4 weeksHRQoL, ease of administration and change in dose from baselineNo significant improvement in HRQoL was measured Subjects preferred the thermostable product The products had similar safety and efficacy profiles
Galiè [20]Riociguat and sildenafilPAH patients on sildenafil therapy17Blinded, randomised controlled and extension study12 weeks, thereafter extensionChange in supine SBP and safetyNo difference in SBP was observed Potentially unfavourable safety signals with sildenafil plus riociguat were observed
Rubin [21]RiociguatPAH396Open-label extension studyMean 95 weeksSafety, 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]RiociguatCTEPH or persistent PH after PEA237Open label extension studyMean 83 weeksSafety, 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 sodiumPAH206Open-label extension studyUp to 24 months6MWDLong-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months
Sitbon [24]Selexipag versus placeboPAH1156Blinded, randomised controlled trialMedian 63.7 weeks (placebo), 70.7 weeks (selexipag)Time-to-event, composite of death or a complication related to PAHThe 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; VO2: 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.