2025 Annual Review of Pulmonary Arterial Hypertension Clinical Research

Pulmonary arterial hypertension (PAH) remains a progressive and life-threatening disease despite major therapeutic advances over the past three decades. Alongside evolving treatment strategies, the growing complexity of PAH management has been accompanied by an expansion of global clinical research activity, creating challenges for clinicians and researchers to synthesize emerging evidence and identify meaningful trends.

This study provides a descriptive analysis of PAH-related clinical studies registered on international platforms integrated into the World Health Organization International Clinical Trials Registry Platform (ICTRP/WHO) between January and December 2025. Trials were characterized according to study design, therapeutic pathway, geographic distribution, funding source, and methodological features, including endpoint selection and incorporation of patient-reported and digital outcomes.

A total of 54 PAH-related studies were registered in 2025, of which 64.8% were interventional and 33.3% observational. Most trials involved pharmacological interventions and were conducted predominantly in high- and middle-income countries, with limited representation from low-income regions. Academic institutions and hospitals accounted for the majority of sponsors, while direct pharmaceutical industry sponsorship was identified in a minority of registrations. Therapeutic investigations extended beyond classical vasodilator pathways, with increased focus on transforming growth factor/bone morphogenetic protein (TGF-β/BMP) signaling modulation, metabolic and cardiorenal pathways, and selective tyrosine kinase inhibition. Methodologically, trials increasingly incorporated composite endpoints, imaging-based assessments, biomarkers, patient-reported outcome measures, and, in a subset, digital health and remote monitoring strategies.

Clinical trials registered in 2025 reflect a PAH research landscape characterized by stable trial volume, diversification of therapeutic targets, and progressive methodological refinement. The growing use of multidimensional endpoints and patient-centered and digital tools suggests a increasing integration of therapeutic response. Persistent gaps in geographic representation and endpoint standardization, however, remain key challenges for the future of PAH clinical research.