Ryo Inuzuka, Taku Ishii, Toru Iwasa, Kenichi Kurosaki, Ayako Kuraoka, Jun Narita, Shinichi Takatsuki, Masayoshi Nakano, Rieko Inagaki, Maki Mihoya, Kim Hyunsoo, Minaka Shibuya, Tohru Kobayashi, Hidekazu Ishida, Taichi Kato, Masaru Miura, Hiroyuki Yamagishi, Shozaburo Doi
University of Tokyo. Institute of Science Tokyo Hospital. National Cerebral and Cardiovascular Center. Fukuoka Children’s Hospital. University of Osaka Graduate School of Medicine. Toho University Omori Medical Center. Johnson & Johnson Innovative Medicine. Jichi Medical University. Nagoya University Graduate School of Medicine. Tokyo Metropolitan Children’s Medical Center. Keio University.
Japan
Circulation Reports
Circ Rep 2026; 8: 1337-1345
DOI: 10.1253/circrep.CR-26-0077
Abstract
Background: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), imposing an increased workload on the right ventricle and ultimately leading to right heart failure. Macitentan is a potent dual endothelin receptor antagonist that blocks both endothelin receptor subtypes A and B, and is approved for adult patients with PAH, but evidence in pediatric PAH patients is limited.
Methods and results: This was an open-label, multicenter, Phase III study enrolling Japanese pediatric PAH patients aged ≥3 months to <15 years. A total of 7 patients were enrolled. Efficacy was evaluated by assessing pulmonary hemodynamics after 24 weeks of treatment, and safety was assessed over a 52-week period. The geometric mean fold change in PVR index (PVRI) at Week 24 was 59.43%, which met the prespecified success criterion of ≤81.6% (primary endpoint). Other pulmonary hemodynamic parameters, including mean PAP, mean right atrial pressure, and total pulmonary resistance, also showed improvement. Additionally, at Week 52, functional outcomes such as 6-minute walk test performance and quality-of-life reports, demonstrated a trend toward improvement. Safety findings were favorable, with no unexpected concerns among the 7 treated participants. Most adverse events were mild to moderate in severity, and none were considered related to macitentan.
Conclusions: Macitentan showed clinically meaningful reduction in PVRI and improved pulmonary hemodynamics in Japanese pediatric patients with PAH, with a favorable safety profile over 52 weeks of treatment.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes