Endpoint design in pulmonary arterial hypertension therapeutic trials permitting pediatric enrollment: a ClinicalTrials.gov registry analysis

Background Pediatric therapeutic development depends not only on age-appropriate dosing but also on endpoints whose administration and interpretation remain coherent across developmental stages. Methods An expanded ClinicalTrials.gov search was performed on 2 October 2026 using pulmonary hypertension terms plus the structured Child age filter (birth–17 years), while restricting eligibility to records first posted on or before 8 August 2026. The combined inventory contained 394 unique records. Seventy-two records formed the main analysis set; 69 were assigned to 57 traceable trial families and three continuation records remained unassigned at family level. Endpoint domains were counted once per family. Results Fifty-two families had registered outcomes available for domain analysis (42 first posted before 2017 and 10 in 2017–2026). Biomarker/laboratory measures occurred in 12/42 versus 9/10 families and functional capacity/activity in 38/42 versus 6/10. The study-level registered maximum permitted age was 18 years or younger in 14/42 earlier and 9/10 later families; this was used only for an age-scope sensitivity stratum and was not an eligibility criterion. In this age-scope stratum, several era contrasts attenuated, including PK/PD/dosing (9/14 vs. 7/9; difference +13.5 percentage points, 95% CI −24.4 to +43.6). A core-primary sensitivity analysis excluding four families whose registry records were updated after the eligibility cutoff produced the same qualitative pattern of no recent functional primary entries and wider uncertainty in the smaller later-era group. Five families with completely missing outcome modules were all in the earlier era; extreme-case analyses are reported in the supplement. Conclusion Endpoint portfolios differed across registration eras, but age-scope composition, differential missingness, and incomplete historical registry reconstruction limit a temporal interpretation. Public endpoint descriptions should specify the clinical construct, measurement method, reporter or data source, capability rule, and handling of children unable to complete an assessment.