Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry. A Candidate Clinical Endpoint

Zijlstra, W. G.; Ploegstra, Mark‐Jan; Vissia-Kazemier, Theresia R.; Roofthooft, Marcus T. R.; Sarvaas, Gideon du Marchie; Bartelds, Beatrijs; Rackowitz, Annette; Heuvel, F. van den; Hillege, Hans L.; Plasqui, Guy; Berger, Rolf M. F.

doi:10.1164/rccm.201608-1576oc

Cited by 38 publications

(36 citation statements)

References 44 publications

(50 reference statements)

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“…For example, the primary efficacy endpoint commonly measured in interventional pulmonary arterial hypertension trials in adults is the 6‐minute walk test (6MWT), which is a measure of exercise capacity . However, the 6MWT would not be a feasible endpoint to measure in infants and young children because they are not developmentally or physically capable of performing the test . In other instances, the relatively small pediatric patient population available or the infrequency of endpoint events often make it unfeasible to incorporate the adult endpoint into a pediatric trial because of the sample size that would be required to achieve adequate statistical power to detect a difference.…”

Section: Discussionmentioning

confidence: 99%

Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA

Green

Burnham

Schuette

et al. 2018

The Journal of Clinical Pharma

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The selection of appropriate endpoints in pediatric drug development trials is a critical aspect of trial design. Given the high pediatric trial failure rate, selecting optimal trial design elements, such as the primary efficacy endpoint, is essential to ensuring increased potential for trial success. The objectives of this study were to identify the primary efficacy endpoints measured in pediatric drug development trials submitted to the US Food and Drug Administration and to relate endpoint attributes to trial and label outcome. The analysis included pediatric pivotal efficacy studies submitted from September 2007 to July 2016 for which there was a corresponding adult trial for the same indication.Two hundred and thirty-four efficacy trials on 138 unique products studied in pediatric patients were assessed. The adult and pediatric endpoints were the same in 141 of the 234 trials (60.3%), and these trials succeeded in meeting their primary endpoint more often (122 of 141 [86.5%]) than when the adult and pediatric endpoints differed (57 of 93 [61.3%]; odds ratio, 4.03; 95%CI, 2.10–7.80). Trials that included both pediatric and adult patients succeeded more frequently than those trials that did not combine pediatric and adult patients (85 of 95 versus 94 of 139, respectively; odds ratio, 4.05; 95%CI, 1.94–9.31). No differences were observed in pediatric trial success between those using subjective and objective endpoints. Using the same endpoint in the pediatric trial as was measured in the corresponding adult trial and enrolling pediatric and adult patients in the same trial were attributes associated with trial success.

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Section: Discussionmentioning

confidence: 99%

Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA

Green

Burnham

Schuette

et al. 2018

The Journal of Clinical Pharma

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“…Monitoring daily physical activity has also been suggested as an alternative tool to assess functional capacity in children. A recent pilot study using three-axis accelerometry in 29 children with PAH and 60 controls showed that physical activity was markedly decreased in children with PAH, and that accelerometer output correlated with clinical disease severity markers and predicted outcome [77]. Larger studies are in progress to validate the use of accelerometry output as a clinically meaningful end-point for clinical trials in paediatric PAH.…”

Section: Updates In Paediatric Ph Epidemiology and Classificationmentioning

confidence: 99%

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

et al. 2019

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Paediatric pulmonary arterial hypertension (PAH) shares common features of adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for the care of children with PAH, as presented by the Paediatric Task Force of the 6th World Symposium on Pulmonary Hypertension. We provide updates of the current definition, epidemiology, classification, diagnostics and treatment of paediatric PAH, and identify critical knowledge gaps. Several features of paediatric PAH including the prominence of neonatal PAH, especially in pre-term infants with developmental lung diseases, and novel genetic causes of paediatric PAH are highlighted. The use of cardiac catheterisation as a diagnostic modality and haemodynamic definitions of PAH, including acute vasoreactivity, are addressed. Updates are provided on issues related to utility of the previous classification system to reflect paediatric-specific aetiologies and approaches to medical and interventional management of PAH, including the Potts shunt. Although a lack of clinical trial data for the use of PAH-targeted therapy persists, emerging data are improving the identification of appropriate targets for goal-oriented therapy in children. Such data will likely improve future clinical trial design to enhance outcomes in paediatric PAH.

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“…Decreased physical activity, as measured by an actigraphy device worn on the wrist of adult PAH patients in the outpatient setting, has been shown to correlate with increased disease severity and worse prognosis [ 98 ]. A more recent study validated this finding in children with PAH, showing a positive correlation between actigraphy-measured physical activity, 6MWD, and improved functional class [ 99 ].…”

Section: Emerging Evaluation Techniquesmentioning

confidence: 69%

Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

Frank

Ivy

2018

Children

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Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed.

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Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry. A Candidate Clinical Endpoint

Cited by 38 publications

References 44 publications

Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA

Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

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