title: Clinical trial design--effect of prone positioning on clinical outcomes in infants and children with acute respiratory distress syndrome.
abstract: OBJECTIVE
  This paper describes the methodology of a clinical trial of prone positioning in pediatric patients with acute lung injury (ALI). Nonrandomized studies suggest that prone positioning improves oxygenation in patients with ALI/acute respiratory distress syndrome without the risk of serious iatrogenic injury. It is not known if these improvements in oxygenation result in improvements in clinical outcomes. A clinical trial was needed to answer this question.
  
  
  METHODS
  The pediatric prone study is a multicenter, randomized, noncrossover, controlled clinical trial. The trial is designed to test the hypothesis that at the end of 28 days, children with ALI treated with prone positioning will have more ventilator-free days than children treated with supine positioning. Secondary end points include the time to recovery of lung injury, organ failure-free days, functional outcome, adverse events, and mortality from all causes. Pediatric patients, 42 weeks postconceptual age to 18 years of age, are enrolled within 48 hours of meeting ALI criteria. Patients randomized to the prone group are positioned prone within 4 hours of randomization and remain prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days. Both groups are managed according to ventilator protocol, extubation readiness testing, and sedation protocols and hemodynamic, nutrition, and skin care guidelines.
  
  
  CONCLUSIONS
  This paper describes the process, multidisciplinary input, and procedures used to support the design of the clinical trial, as well as the challenges faced by the clinical scientists during the conduct of the clinical trial.
authors.affiliation: Critical Care and Cardiovascular Nursing, Children's Hospital, Boston, MA 02115, USA. martha.curley@childrens.harvard.edu
authors.forename: Martha A Q
authors.initials: MA
authors.lastname: Curley
authors.forename: John H
authors.initials: JH
authors.lastname: Arnold
authors.forename: John E
authors.initials: JE
authors.lastname: Thompson
authors.forename: James C
authors.initials: JC
authors.lastname: Fackler
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Grant
authors.forename: Lori D
authors.initials: LD
authors.lastname: Fineman
authors.forename: Natalie
authors.initials: N
authors.lastname: Cvijanovich
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Barr
authors.forename: Shirley
authors.initials: S
authors.lastname: Molitor-Kirsch
authors.forename: David M
authors.initials: DM
authors.lastname: Steinhorn
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hibberd
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D017063:Outcome Assessment, Health Care; D016684:Prone Position; D012107:Research Design; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*; D016683:Supine Position