Sun Haihao, Stockbridge Norman, Ivy D Dunbar, Clark Jennifer, Bates Angela, Handler Stephanie S, Krishnan Usha S, Mullen Mary P, Yung Delphine, Hopper Rachel K, Varghese Nidhy P, Avitabile Catherine M, Fineman Jeff, Austin Eric D, Freire Grace
Office of the Commissioner, U.S. Food and Drug Administration (FDA), Silver Spring, MD.
Office of the Commissioner, U.S. Food and Drug Administration (FDA), Silver Spring, MD.
J Pediatr. 2025 Feb;277:114383. doi: 10.1016/j.jpeds.2024.114383. Epub 2024 Nov 1.
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 6-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.
We conducted a prospective, multicenter, noninterventional study in pediatric PAH patients and healthy children. Actiheart and Fitbit Charge 2 recorded pA and heart rate data. HRV was defined as SD of daily heart rate. 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 vs II. Power/sample size simulations were conducted to detect hypothetical treatment effect equivalent to differences seen between FC III and FC II.
We enrolled 116 children: 90 and 98 adhered with Actiheart and Fitbit, respectively. Actigraphy daily pA was ∼36% lower (P < .05) and daily HRV was ∼18% lower (P < .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.
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.
探讨使用活动记录仪测量身体活动（pA）和心率变异性（HRV）作为儿科肺动脉高压（PAH）研究终点的可行性，并将其性能与6分钟步行距离（6MWD）进行比较，6MWD是成人和能够行走并理解测试过程的儿童PAH临床试验中常用的主要终点。
我们对儿科PAH患者和健康儿童进行了一项前瞻性、多中心、非干预性研究。Actiheart和Fitbit Charge 2记录pA和心率数据。HRV定义为每日心率的标准差。分析同一受试者的活动记录仪pA、HRV和6MWD，以比较PAH儿童与对照组，以及巴拿马功能分级（FC）III级与II级。进行了功效/样本量模拟，以检测相当于FC III级和II级之间差异的假设治疗效果。
我们招募了1|6名儿童：分别有90名和98名儿童坚持使用Actiheart和Fitbit。PAH儿童（n = 62）的活动记录仪每日pA比健康对照组（n = 54）低约36%（P <.05），每日HRV低约18%（P <.05）。FC III级的每日pA和每日HRV比FC II级低约17%，而6MWD差异不大。功效为80%时的模拟显示，检测差异/效果时，pA每组需要175名受试者，HRV每组需要40名受试者，而6MWD需要超过我们200的最大样本量。
活动记录仪在儿科PAH中是一种可行的测量方法。与6MWD相比，pA和HRV在区分巴拿马FC III级和II级方面可能更敏感。HRV可能会提高活动记录仪在儿科PAH中的效用。
