title: Assessment of measurement properties of peak VO(2) in children with pulmonary arterial hypertension.
abstract: BACKGROUND
  The 6-minute walk test evaluates the effect of pharmacologic intervention in adults with pulmonary arterial hypertension (PAH) but, for reasons of compliance or reliability, may not be appropriate for children at all ages. Thus, peak oxygen consumption (VO2, maximal exercise test) was used instead in a pediatric PAH trial (STARTS-1) to evaluate pharmacologic intervention with sildenafil. This was the first large placebo-controlled trial to use the peak VO2 endpoint in this population. Our working hypothesis was that, as with other populations, percentage changes in peak VO2 in pediatric patients with PAH are reliable and are associated with changes in other clinical endpoints.
  
  
  METHODS
  Using data from the subpopulation of 106 patients who were developmentally and physically able to perform exercise testing, all of whom were World Health Organization Functional Class (WHO FC) I, II, or III, reliability was assessed using the intraclass correlation coefficient and Bland-Altman plot on screening and baseline data. Relationships between percentage change in peak VO2 from baseline to end of treatment and other endpoints were evaluated using correlation coefficients and regression analyses.
  
  
  RESULTS
  The intraclass correlation was 0.79 between screening and baseline peak VO2, an agreement that was supported by the Bland-Altman plot. Percentage change in peak VO2 correlated well (r ≥0.40) and showed responsiveness to a physician global assessment of change and with change in WHO FC (for baseline classes I and III). Percentage change in peak VO2 did not correlate with change in the Family Cohesion of the Child Health Questionnaire (r = 0.04) or with a subject global assessment of change (r = 0.12). The latter may have been influenced by child and parental-proxy response and instrument administration.
  
  
  CONCLUSIONS
  In pediatric PAH patients who are developmentally and physically able to perform exercise testing, peak VO2 measurements exhibited good reliability and improvements that were associated with improvements in certain other clinical endpoints, such as the WHO FC and a physician global assessment.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00159913.
authors.affiliation: Department of Statistics, Pfizer Inc, Groton, CT, USA. joseph.c.cappelleri@pfizer.com
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.forename: Lie-Ju
authors.initials: LJ
authors.lastname: Hwang
authors.forename: Jack
authors.initials: J
authors.lastname: Mardekian
authors.forename: Marko A
authors.initials: MA
authors.lastname: Mychaskiw
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D023381:Endpoint Determination; D005080:Exercise Test; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D015203:Reproducibility of Results; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016138:Walking / Q000502:physiology
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate