Actigraphy Study Endpoints to Reduce Sample Size and Facilitate Drug Development for Pediatric Pulmonary Arterial Hypertension.

Autor: Sun H; Office of the Commissioner, U.S. Food and Drug Administration (FDA). Electronic address: haihao.sun@fda.hhs.gov., Stockbridge N; Office of the Commissioner, U.S. Food and Drug Administration (FDA)., Ivy DD; Section of Cardiology, Department of Pediatrics, University of Colorado School of Medicine., Clark J; Office of the Commissioner, U.S. Food and Drug Administration (FDA)., Bates A; Stollery Children's Hospital, Department of Pediatrics, University of Alberta., Handler SS; Department of Pediatrics, Division of Cardiology, Medical College of Wisconsin., Krishnan US; New York Presbyterian Hospital and Columbia University Irving Medical Center., Mullen MP; Boston Children's Hospital; Harvard Medical School., Yung D; University of Washington School of Medicine and Seattle Children's Hospital., Hopper RK; Stanford University School of Medicine and Lucile Packard Children's Hospital., Varghese NP; Baylor College of Medicine and Texas Children's Hospital., Avitabile CM; Children's Hospital of Philadelphia, University of Pennsylvania., Fineman J; UCSF Benioff Children's Hospital., Austin ED; Vanderbilt University., Freire G; Johns Hopkins All Children's Hospital in St Petersburg, FL.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2024 Nov 01, pp. 114383. Date of Electronic Publication: 2024 Nov 01.
DOI: 10.1016/j.jpeds.2024.114383
Abstrakt: Objectives: To investigate the feasibility of using actigraphy to measure physical activity (pA) and heart rate variability (HRV) as study endpoints in pediatric pulmonary arterial hypertension (PAH) and to compare their performance to six-minute-walk distance (6MWD), a common primary endpoint used in PAH clinical trials in adults and children who can walk and understand the test process.
Study Design: We conducted a prospective, multicenter, non-interventional study in pediatric PAH patients and healthy children. Actiheart™ and Fitbit Charge 2™ recorded pA and heart rate (HR) data. HRV was defined as standard deviation of daily HR. Actigraphy pA and HRV and 6MWD from the same subjects were analyzed to compare children with PAH with controls, and Panama functional classification (FC) III versus II. Power/sample size simulations were conducted to detect hypothetical treatment effect equivalent to differences seen between FC III and FC II.
Results: We enrolled 116 children; 90 and 98 adhered with Actiheart and Fitbit, respectively. Actigraphy daily pA was ∼36% lower (P<0.05) and daily HRV was ∼18% lower (P<0.05) in children with PAH (n=62) than healthy controls (n=54). Daily pA and daily HRV trended ∼17% lower in FC III than FC II, whereas 6MWD showed little difference. Simulation at 80% power showed that pA required 175 subjects per group and HRV required 40 per group to detect the difference/effect, whereas 6MWD required over our maximum sample size of 200.
Conclusions: Actigraphy is a feasible measure in pediatric PAH. Compared with 6MWD, pA and HRV may be more sensitive in differentiating Panama FC III from II. HRV may improve actigraphy's utility in pediatric PAH.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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