Lancet
Prone positioning and high-frequency oscillatory ventilation in early paediatric acute respiratory distress syndrome (PROSpect): an international, two-by-two factorial, response-adaptive, phase 3, randomised controlled trial
By Curley MAQ, Kneyber MCJ, Cheifetz IM and 20 others.
Abstract
Background
Data on prone positioning and high-frequency oscillatory ventilation (HFOV) used separately or in combination in patients with paediatric acute respiratory distress syndrome (PARDS) are inconclusive, leading to wide practice variability. We aimed to compare the effects of prone positioning with supine positioning and the effects of HFOV with conventional mechanical ventilation on ventilator-free days in children with early, moderate-to-severe PARDS.
Methods
PROSpect was an international, two-by-two factorial, response-adaptive, phase 3, randomised controlled trial done in 75 paediatric intensive care units in 18 countries. Eligible patients were aged 2 weeks to 20 years, and were intubated and mechanically ventilated for less than 96 h before meeting criteria for moderate-to-severe PARDS. Patients were centrally randomly assigned using a web-based system to supine positioning and conventional mechanical ventilation, prone positioning and conventional mechanical ventilation, supine positioning and HFOV, or prone positioning and HFOV. Initially, the allocation was 1:1:1:1 stratified by age group and direct or indirect lung injury using a permuted block design with blocks of four and eight. Response-adaptive randomisation updates were planned to adjust allocation probabilities 28 days after 300 patients were randomly assigned and then 28 days after every 100 additional patients. Given the nature of the interventions, masking was not possible. The primary outcome was ventilator-free days through to day 28 among all randomly assigned participants. Safety was assessed prospectively by daily monitoring for the occurrence of prespecified adverse events. This study was registered with ClinicalTrials.gov (NCT03896763) and is closed to enrolment.