Assessing Daily Life Physical Activity by Actigraphy in Pulmonary Arterial Hypertension: Insights From the Randomized Controlled Study With Selexipag (TRACE)

Luke S Howard, Stephan Rosenkranz, Robert P Frantz, Anna R Hemnes, Thomas Pfister, Shu-Fang Hsu Schmitz, Hall Skåra, Marc Humbert, Ioana R Preston, Luke S Howard, Stephan Rosenkranz, Robert P Frantz, Anna R Hemnes, Thomas Pfister, Shu-Fang Hsu Schmitz, Hall Skåra, Marc Humbert, Ioana R Preston

Abstract

Background: Reduced daily life physical activity (DLPA) in pulmonary arterial hypertension (PAH) contributes to a poor quality of life.

Research question: Can actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo?

Study design and methods: Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension (TRACE) was a prospective, multicenter, randomized, placebo-controlled, double-blind, exploratory phase 4 study enrolling patients with PAH in World Health Organization functional class II/III, receiving stable endothelin receptor antagonist with/without phosphodiesterase type 5 inhibitor background therapy. Primary end points were change from baseline to Week 24 in actigraphy-assessed DLPA (recorded by using an accelerometer), including daily time spent in nonsedentary physical activity (NSPA), daily time spent in moderate to vigorous physical activity (MVPA), daily volume of activity, and daily number of steps.

Results: At baseline, patients (N = 108) were prevalent, on stable background PAH therapy, and at low risk of disease progression. Patients showed high compliance with wear of the accelerometer throughout the study. From baseline to Week 24, mean daily time spent in NSPA increased by 1.1 min and decreased by 16.7 min in the selexipag and placebo groups (treatment difference [95% CI], 17.8 [-6.0, 41.6] min); mean time spent in MVPA increased by 0.3 min and was reduced by 2.0 min in the selexipag and placebo groups (treatment difference [95% CI], 2.3 [-10.8, 15.4] min); and mean number of daily steps decreased by 0.3 and 201.9 in the selexipag and placebo groups (treatment difference [95% CI], 201.6 [-243.0, 646.2]).

Interpretation: TRACE enrolled a prevalent population on background therapy and at low risk of disease progression. Changes in DLPA were small and highly variable, with no statistically significant differences between treatment groups. This patient-centric study was the first randomized trial in PAH to capture high-quality actigraphy data and to describe DLPA in terms of mean/median and variability, which may inform the design of future studies.

Clinical trial registration: ClinicalTrials.gov; No.: NCT03078907; URL: www.

Clinicaltrials: gov.

Keywords: actigraphy; daily life physical activity; pulmonary arterial hypertension; quality of life; selexipag.

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Patient disposition. Eleven patients were not randomized to treatment: nine because they did not meet inclusion/exclusion criteria and two because of physician’s decision. Five patients in the selexipag group and zero patients in the placebo group discontinued due to prostacyclin-associated adverse events.
Figure 2
Figure 2
Change from baseline to Week 24 in daily time spent in NSPA (A), daily time spent in MVPA (B), and daily number of steps during wake time (C). aChange from baseline and treatment difference are estimated by analysis of covariance model with baseline value as covariate. MVPA = moderate to vigorous physical activity; NSPA = nonsedentary physical activity.

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