Features of Chronic Thromboembolic Pulmonary Hypertension Clinical Trials

Purpose Innovative research in diagnosis and treatment have led to a rapid evolution in CTEPH care. The purpose of this study is to analyze completed and ongoing CTEPH clinical trials to inform future investigation. Methods The ClinicalTrials.gov database and the World Health Organization International Clinical Trials Registry Platform (ICTRP) were searched for “CTEPH” and related terms up to July 2020. PubMed was searched for all trial numbers to identify associated publications. Results There were 107 entries in ClinicalTrials.gov and 126 in ICTRP, with 132 total after removing duplicates/non-target entries. 63 trials were pharmaceutical (n=48) and/or procedural (n=19) interventions for treatment of CTEPH, 52% industry-sponsored, and 56% early phase, when specified. The most frequent pharmaceutical interventions were riociguat (35%), macitentan (19%), bosentan (10%), and selexipag (10%). The most frequent procedures were balloon pulmonary angioplasty (63%), pulmonary endarterectomy (16%), and pulmonary artery denervation (11%). Procedural trials were more frequently randomized than pharmaceutical trials. 272 outcomes were listed, 41 unique, with 6-minute walk distance (6MWD) as the most frequent (31/272; 11%). Other trials included investigation of incidence (n=18), imaging (n=8), exercise (n=8), oxygen/ventilation (n=8), registries (n=15), and others (n=12). The most frequent affiliation (country) of the principal investigator, for all 132 entries, was Japan (n=23; 17%). For pharmaceuticals it was USA and procedures it was China. Recruitment targets ranged up to 1301 participants with 41% still recruiting and 2% terminated early. 44 publications, including 27 articles of original research, were identified searching for all 132 trial identifiers. Conclusion CTEPH clinical trials are most commonly pharmaceutical, early phase and industry-sponsored with a 6MWD outcome. There is substantial variation in design and regional approach with a minority of trial results found in peer-reviewed literature.