Assessing Daily Life Physical Activity by Actigraphy in Pulmonary Arterial Hypertension

Abstract

BackgroundReduced daily life physical activity (DLPA) in pulmonary arterial hypertension (PAH) contributes to a poor quality of life.Research QuestionCan actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo?Study Design and MethodsEffect 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.ResultsAt 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]).InterpretationTRACE 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 RegistrationClinicalTrials.gov; No.: NCT03078907; URL: www.clinicaltrials.gov Reduced daily life physical activity (DLPA) in pulmonary arterial hypertension (PAH) contributes to a poor quality of life. Can actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo? 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. 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]). 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. ClinicalTrials.gov; No.: NCT03078907; URL: www.clinicaltrials.gov Take-home PointsStudy Question: Can actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo in the exploratory phase 4 TRACE RCT?Results: Patients showed high compliance with wear of the accelerometer throughout the study, and small changes in DLPA parameters were observed in the selexipag and placebo groups.Interpretation: TRACE is the first randomized trial in PAH to successfully collect high-quality actigraphy data. Although changes in DLPA were small and highly variable, high patient compliance supports the potential for monitoring DLPA in future clinical trials. Study Question: Can actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo in the exploratory phase 4 TRACE RCT? Results: Patients showed high compliance with wear of the accelerometer throughout the study, and small changes in DLPA parameters were observed in the selexipag and placebo groups. Interpretation: TRACE is the first randomized trial in PAH to successfully collect high-quality actigraphy data. Although changes in DLPA were small and highly variable, high patient compliance supports the potential for monitoring DLPA in future clinical trials. Pulmonary arterial hypertension (PAH) is a rare and debilitating disease affecting the pulmonary vasculature that can lead to right heart failure.1Vonk Noordegraaf A. Galiè N. The role of the right ventricle in pulmonary arterial hypertension.Eur Respir Rev. 2011; 20: 243-253Crossref PubMed Scopus (189) Google Scholar PAH affects all aspects of a patient’s life2Delcroix M. Howard L. Pulmonary arterial hypertension: the burden of disease and impact on quality of life.Eur Respir Rev. 2015; 24: 621-629Crossref PubMed Scopus (117) Google Scholar and is characterized by nonspecific symptoms such as reduced exercise capacity and dyspnea.3Taichman D.B. Shin J. Hud L. et al.Health-related quality of life in patients with pulmonary arterial hypertension.Respir Res. 2005; 6: 92Crossref PubMed Scopus (161) Google Scholar Physical activity is defined as any bodily movement produced by skeletal muscles that results in energy expenditure and in daily life can be categorized into occupational, household, conditioning, sports, or other activities.4Caspersen C. Powell K. Christenson G.M. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research.Public Health Reports. 1985; 100: 126-131PubMed Google Scholar Physical activity is associated with a reduced risk of morbidity/mortality across a range of cardiovascular diseases, and the benefits of physical activity seem greater in those with cardiovascular disease vs those without.5Kim M.-H. Sung J.-H. Jin M.-N. et al.Impact of physical activity on all-cause mortality according to specific cardiovascular disease.Frontiers Cardiovasc Med. 2022; 9: 811058Crossref PubMed Scopus (5) Google Scholar,6Jeong S.-W. Kim S.-H. Kang S.-H. et al.Mortality reduction with physical activity in patients with and without cardiovascular disease.Eur Heart J. 2019; 40: 3547-3555Crossref PubMed Scopus (132) Google Scholar Structured tests such as the 6-min walk test typically used to assess the exercise ability of patients with PAH provide a snapshot of physical capacity at the time of the test but do not reflect daily life physical activity (DLPA).7Pugh M.E. Buchowski M.S. Robbins I.M. et al.Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension.Chest. 2012; 142: 1391-1398Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar The measurement of DLPA allows for continuous evaluation, providing a more comprehensive overview of a patient’s physical activity than a single measurement, yet DLPA is not commonly assessed in PAH trials. Reduced DLPA in patients with PAH7Pugh M.E. Buchowski M.S. Robbins I.M. et al.Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension.Chest. 2012; 142: 1391-1398Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 8Halliday S.J. Shi H. Brittain E.L. et al.Reduced free-living activity levels in pulmonary arterial hypertension patients.Pulm Circ. 2019; 92045894018814182Crossref PubMed Scopus (9) Google Scholar, 9Mainguy V. Provencher S. Maltais F. et al.Assessment of daily life physical activities in pulmonary arterial hypertension.PLoS One. 2011; 6e27993Crossref PubMed Scopus (75) Google Scholar can substantially affect health-related quality of life.3Taichman D.B. Shin J. Hud L. et al.Health-related quality of life in patients with pulmonary arterial hypertension.Respir Res. 2005; 6: 92Crossref PubMed Scopus (161) Google Scholar,7Pugh M.E. Buchowski M.S. Robbins I.M. et al.Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension.Chest. 2012; 142: 1391-1398Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Patients with PAH were found to have lower for physical and of the Health with the D.B. Shin J. Hud L. et al.Health-related quality of life in patients with pulmonary arterial hypertension.Respir Res. 2005; 6: 92Crossref PubMed Scopus (161) Google Scholar and lower DLPA associated with greater and physical H. et al.Physical activity and symptoms in pulmonary arterial hypertension.Chest. Full Text Full Text PDF PubMed Scopus Google Scholar reduced health-related quality of life as measured by using the Health is associated with in patients with et al.Health-related quality of life and in pulmonary arterial PubMed Scopus Google Scholar reduced physical activity to increased which affect patients with L. A. C. et al.Physical activity levels low in patients with pulmonary Med. 6: PubMed Google Scholar for patient-centric that on more including a in physical capacity for daily L. S. and of for pulmonary arterial hypertension: do Respir Rev. PubMed Scopus Google Scholar is a for physical J. S. of the Scopus Google Scholar measurement of DLPA with actigraphy may provide an of physical activity and clinical not as a end in PAH clinical trials. is to assess DLPA in a randomized trial to potential changes in physical activity in a the Selexipag in Pulmonary Arterial Hypertension the receptor selexipag was to the risk of a morbidity/mortality by with placebo in a population of patients with et for the treatment of pulmonary arterial Med. 2015; PubMed Scopus Google Scholar on selexipag was for the treatment of PAH in patients with World Health Organization functional class to of a of and Scholar Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension (TRACE) to actigraphy be used to assess changes in DLPA in patients with PAH receiving selexipag or placebo in an The of of is at on for to the study data can be the at TRACE was a prospective, multicenter, randomized, placebo-controlled, exploratory phase 4 study, on and on of Health Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension of Scholar The in with the a of and the of the trial and the data. was from and the study was in compliance with the of was from all enrolled DLPA and quality of data were to a baseline of to Patients were randomized to selexipag or placebo for 24 on the and is in and Selexipag was as et for the treatment of pulmonary arterial Med. 2015; PubMed Scopus Google Scholar of study was a Patients to with PAH and or associated with or heart disease by right heart N. M. et for the and treatment of pulmonary hypertension: the for the and of Pulmonary Hypertension of the of and the for and for Heart and Respir J. 2015; PubMed Scopus Google N. M. et for the and treatment of pulmonary hypertension: the for the and of Pulmonary Hypertension of the of and the for and for Heart and Heart J. PubMed Scopus Google Scholar were Patients were to have a 6-min walk and be in to without or in the to Patients to be receiving an endothelin receptor antagonist or in with a phosphodiesterase type 5 inhibitor or for and at a stable for to in an was not in the to study or at any the study. Full in on Week and Week 24, and patients were from the the as as at and DLPA was with a accelerometer et of the physical activity to accelerometry measured physical activity and PubMed Scopus Google Scholar, J. and of activity and for physical activity in Med. PubMed Scopus Google Scholar, K. C. of to and One. 2019; PubMed Scopus Google Scholar Patients were to wear the on the of for the of the study, 24 and a of the actigraphy a was defined as a with at of At in a were used for the and time were et al.Physical activity in the measured by 40: PubMed Scopus Google Scholar, et from PubMed Scopus Google Scholar, C. et accelerometer for time from physical activity or PubMed Scopus Google Scholar data were in of activity for and for and all actigraphy were across from baseline to first to Week 24 data were daily the wear time monitoring by the study and of patients for was to compliance Patients were to activity data and not to physical The Pulmonary Arterial and is a that symptoms and M. et of the Pulmonary Arterial and results of the Full Text Full Text PDF PubMed Scopus Google S. D.B. et of the Pulmonary Arterial and a for Res. PubMed Scopus Google Scholar was at baseline, Week and Week using the and levels were assessed and at and was assessed at all and were the end of study TRACE was as an exploratory study with a on and all actigraphy were end Primary end points were change from baseline to Week 24 in actigraphy-assessed which daily time spent in nonsedentary physical activity and of and daily physical DLPA end points were and to NSPA defined as activity et A. et of between and and PubMed Scopus Google and activity et et of time spent in in the PubMed Scopus Google to as of the et J. of the and PubMed Scopus Google and time spent in moderate to vigorous physical activity defined as activity et J. of the and PubMed Scopus Google et J. of the and PubMed Scopus Google Scholar measured activity using a from the accelerometer used in TRACE were by to with the Daily number of as a measurement of daily activity, was by using for DLPA end points in end points change from baseline to Week 24 in and TRACE was to be was no or for The of patients was on on is in from baseline to Week 24 and treatment difference in and were by using an of with a for baseline from baseline mean and treatment difference for were by using an of with a for baseline was at baseline and Week of treatment with the from baseline between and DLPA parameters and number of daily at baseline, Week and Week 24 was in the population using the data at Week 24 to were with the in the and end actigraphy data at Week were by using a with were by using From to a of patients were across in patients were randomized to selexipag and patients to placebo baseline for groups were with the of a of patients and in the selexipag The population was prevalent time from with on background therapy. 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The high of patient compliance in TRACE the of using to patients with PAH an TRACE a prevalent population of PAH patients with and levels of low risk and with the in no or small changes in functional and were observed at Week 24 in the placebo no significant disease the 24 of the study. was observed in the selexipag The time small and small may have the of treatment the study, which enrolled a PAH population (N = with more selexipag reduced the risk of disease by with a treatment on of at Patients in were for a of time than those in TRACE to vs et for the treatment of pulmonary arterial Med. 2015; PubMed Scopus Google Scholar in a phase trial of patients with PAH receiving stable endothelin receptor antagonist a phosphodiesterase type 5 inhibitor therapy, treatment with selexipag with a treatment on pulmonary of at and an in mean from baseline by in the selexipag A. et an receptor for the treatment of pulmonary arterial hypertension.Eur Respir J. 2012; 40: PubMed Scopus Google Scholar for selexipag in TRACE was in with that observed in et for the treatment of pulmonary arterial Med. 2015; PubMed Scopus Google Scholar and the of patients the study. and changes in DLPA were observed in and clinical yet to be results can be used to inform the of actigraphy for the measurement of DLPA in future trial was a difference in the daily time spent in NSPA between the defined by et A. et of between and and PubMed Scopus Google Scholar and et J. of the and PubMed Scopus Google Scholar vs and vs in the selexipag and placebo in PAH have levels of daily from S. M. et actigraphy in patients with pulmonary PubMed Scopus Google Scholar to of daily time min of which was L. A. C. et al.Physical activity levels low in patients with pulmonary Med. 6: PubMed Google Scholar to of moderate activity with of et role of an activity in the of patients with pulmonary Respir J. PubMed Scopus Google Scholar that the type of and the of activity levels can between is to to the results in NSPA using the defined by et A. et of between and and PubMed Scopus Google Scholar may be more that was using the and used in the defined by et J. of the and PubMed Scopus Google Scholar was for with a study patients with PAH of time in activity using a activity was not H. et al.Physical activity and symptoms in pulmonary arterial hypertension.Chest. Full Text Full Text PDF PubMed Scopus Google Scholar can be to activity time using a This the for across used in future to between studies. with H. et al.Physical activity and symptoms in pulmonary arterial hypertension.Chest. Full Text Full Text PDF PubMed Scopus Google S. M. C. et al.Physical activity in patients with pulmonary arterial and 2019; PubMed Scopus Google S. Activity in pulmonary Med. 2019; Full Text Full Text PDF PubMed Scopus Google Scholar the results of the between and DLPA parameters the of daily number of steps to exercise capacity in a daily life and be as an end in clinical studies. the and difference of DLPA parameters in PAH have not in TRACE was on population and may be for future trials. in PAH that patients have a to the by the M.E. Buchowski M.S. Robbins I.M. et al.Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension.Chest. 2012; 142: 1391-1398Abstract Full Text Full Text PDF PubMed Scopus (62) Google S.J. Shi H. Brittain E.L. et al.Reduced free-living activity levels in pulmonary arterial hypertension patients.Pulm Circ. 2019; 92045894018814182Crossref PubMed Scopus (9) Google Scholar Patients with PAH to a of physical activity may not activity not M.S. et of with on with a randomized clinical Scopus Google Scholar The that TRACE patients were not to activity may have to the changes to DLPA for patients with PAH can in an increased of S. et to physical activity in pulmonary arterial hypertension.Chest. Full Text Full Text PDF PubMed Scopus Google Scholar which be in future in which DLPA is measured to a treatment to physical activity by patients with PAH of of and of in V. C. et al.Physical activity and health-related quality of life in patients with pulmonary 2019; Google Scholar and to be in future trials. The high levels of compliance observed in TRACE provide that DLPA can be and used successfully in clinical in a clinical trial TRACE the potential for data in future with the of actigraphy and to study the burden of study the a time data monitoring such yet more of DLPA in PAH clinical can the and functional end points and of patients and which patients and the exploratory of the the results be with DLPA end points were to the of the and in J. The of and on physical a PubMed Scopus Google Scholar which may have changes in physical activity and to the high in the data. the study of 24 may not have for the on quality of life and physical activity to that of selexipag to a a TRACE was a exploratory and study using actigraphy-assessed DLPA as end and was the first randomized trial in patients with PAH to collect high-quality actigraphy data. This supports the potential for monitoring DLPA in future clinical trials. to the of actigraphy in on aspects such as patient of of end and to physical This study was by a of

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