Pathological Mechanisms and Potential Therapeutic Targets of Pulmonary Arterial Hypertension: A Review

Xiao Ying, Chen Pei-Pei, Zhou Rui-Lin, Zhang Yang, Tian Zhuang, Zhang Shu-Yang

Table 2 Clinical trials and potential therapeutic targets in pulmonary arterial hypertension.

Drug/agent Mechanism ClinicalTrials.gov identifier Participants Study design Study duration Primary outcome measure Outcome Tacrolimus (FK506) Activator of BMP signaling NCT01647945 23 patients with PAH Single center, phase II randomized, placebo-controlled study 16 weeks Safety of low-dose FK-506 in PAH Completed Tocilizumab Humanized anti-IL6R antibody NCT02676947 29 patients with group 1 PAH Open-label phase II trial 6 months Safety in terms of the incidence and severity of adverse events Completed Anakinra Recombinant IL-1 receptor antagonist NCT03057028 6 patients with stable PAH and RV failure Single-arm, open-label, phase IB/II pilot study 14 days Change in exercise capacity as determined by peak oxygen consumption and ventilatory efficiency Completed Rituximab Anti-CD20 antibody NCT01086540 SSc-PAH Double-blind, placebo-controlled, phase II, multicenter, randomized trial 48 weeks Change from baseline in 6MWD Active, not recruiting Dichloroacetic acid (DCA) Inhibition of pyruvate dehydrogenase kinase NCT01083524 20 adult patients with IPAH Phase I, open-label, two-center study 28 weeks Safety and tolerability of DCA Completed Apabetalone (RVX-208) BET inhibitor NCT03655704 Estimated 10 participants Early phase I, two-center, open-label trial 16 weeks Change in PVR Recruiting Olaparib PARP1 inhibitor NCT03251872 Estimated 6 participants Open-label, early phase I trial 16 weeks Change in PVR Recruiting Anastrozole Estrogen inhibitor NCT01545336 18 participants Double-blind, placebo-controlled, phase II study 3 months Plasma estradiol (E2) level, tricuspid annular plane systolic excursion (TAPSE) Completed Metformin Multifunctional aromatase inhibitor and AMPK activator NCT03617458 160 participants Phase II, 2×2 factorial, randomized, blinded trial 12 weeks Change from baseline in 6MWD Recruiting Imatinib Selective tyrosine kinase inhibitor NCT01392495 17 participants Open-label, phase III, nonrandomized trial 144 weeks Number of patients with adverse event and deaths Terminated for severe adverse effects Dimethyl fumarate Nuclear factor erythroid 2-related factor 2 (Nrf2) activator NCT02981082 34 participants with SSc-PAH Double-blinded, phase I, placebo-controlled pilot study 24 weeks Improvement in 6MWD Recruiting Bardoxolone methyl Nrf2 pathway-activating agent NCT02657356 202 participants with CTD-PAH Phase III, double-blind, randomized, placebo-controlled trial 24 weeks Change from baseline in 6MWD Not recruiting Gene-enhanced EPCs (PHACeT trial) Cell therapy NCT00469027 7 participants with PAH Phase I, open-label, dose-escalation study 5 years Tolerability and safety of the injection of genetically engineered progenitor cells Completed Pulmonary artery denervation (PADN) Inhibitor of sympathetic stimulation NCT02284737 Estimated 270 participants Phase IV, prospective, multicenter, randomized control trial 6 months PAH-related events, death including lung transplantation, atrial septostomy, worsening of PAH Recruiting