TABLE 1

Potential pulmonary arterial hypertension (PAH) therapies currently in development

Therapy	Clinical trial identifier	Clinical trial design	Primary end-points	Treatment duration	Status (October 2016)
Therapies targeting inflammation and immunity
Ubenimex	NCT02664558	Phase II, multicentre, randomised, double-blind, placebo-controlled trial in PAH patients	Change in PVR	24 weeks	Recruiting [17]
Ubenimex	NCT02736149	Phase II, open-label, multicentre, extension study in PAH patients	Frequency of adverse events	∼1 year	Not yet recruiting [18]
Rituximab	NCT01086540	Phase II, randomised, double-blind, placebo-controlled trial in PAH-SSc patients	Change in PVR	24 weeks	Recruiting [19]
Tocilizumab	NCT02676947	Phase II, open-label trial in PAH patients	Incidence and severity of adverse events; change in PVR	6 months	Recruiting [20]
Therapies targeting mitochondrial dysfunction
Bardoxolone methyl	NCT02036970	Phase II, double-blind, randomised, interventional trial in pulmonary hypertension Group I, II or V patients	Change in 6MWD	16 weeks	Preliminary results published [21]
Bardoxolone methyl	NCT02657356	Phase III, double-blind, early interventional trial in PAH-CTD patients	Change in 6MWD	24 weeks	Recruiting [22]
GS-4997	NCT02234141	Phase II, dose-ranging, randomised, double-blind, placebo-controlled trial in PAH patients	Change in PVR	24 weeks	Ongoing, not recruiting [23]
Therapies targeting BMPR2 signalling
Tacrolimus	NCT01647945	Phase II, double-blind, randomised trial in PAH patients	Frequency of adverse events	16 weeks	Terminated due to limited funding/slow patient recruitment; follow-up multicentre phase IIb efficacy trial planned [24]
Therapies targeting iron deficiency
Ferinject (ferric carboxymaltose)	NCT01447628	Phase II, double-blind, randomised, interventional trial in IPAH, HPAH and anorexigen-associated PAH patients	Change in PVR and exercise capacity	24 weeks	Recruiting [25]
Ferinject (ferric carboxymaltose)	NCT01847352	Single-blind, nonrandomised, interventional, trial in healthy volunteers who met iron-deficient or iron-replete criteria	Change in PASP following i.v. iron infusion	1 week	Completed: April 2014 [26, 27]
Ferrous sulfate (oral dietary iron supplement)	NCT01446848	Interventional, open-label study in IPAH patients with iron deficiency	Change in zinc protoporphyrin level; change in serum ferritin level	12 weeks	Completed: August 2014 [28]
Pulmonary artery denervation
Pulmonary arterial denervation procedure	chiCTR-ONC-12002085	Phase II, observational, unblinded, nonrandomised study in PAH and PAH-CTD patients	Change in PASP and 6MWD	24 weeks	Completed: April 2014 [29]
Pulmonary arterial denervation procedure	NCT02525926	Single-blind, randomised, interventional efficacy study in PAH patients	Mean pulmonary artery pressure	26 weeks	Recruiting [30]

PVR: pulmonary vascular resistance (as measured by right heart catheterisation); PAH-SSc: PAH associated with systemic sclerosis; 6MWD: 6-min walk distance; PAH-CTD: PAH associated with connective tissue disease; BMPR2: bone morphogenetic protein receptor type 2; IPAH: idiopathic PAH; HPAH: heritable PAH; PASP: pulmonary artery systolic pressure.