Protocol for the Prone and Oscillation Pediatric Clinical Trial ( PROSpect ).

Area of Science:

• Critical Care Medicine
• Pediatric Pulmonology
• Clinical Trials Methodology

Background:

• Current respiratory management for pediatric acute respiratory distress syndrome (PARDS) is primarily supportive.
• Limited data exists to guide the choice between supine and prone positioning (PP) or conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV).

Purpose of the Study:

• To compare the efficacy of prone positioning (PP) versus supine positioning and high-frequency oscillatory ventilation (HFOV) versus conventional mechanical ventilation (CMV) in pediatric patients with moderate-to-severe PARDS.
• To provide evidence-based guidance for respiratory management strategies in critically ill children.

Main Methods:

• A global, multicenter, two-by-two factorial, response-adaptive randomized controlled trial (PROSpect) involving approximately 60 PICUs.
• Pediatric patients (≥2 weeks old) with moderate-to-severe PARDS randomized to one of four arms: supine/CMV, prone/CMV, supine/HFOV, or prone/HFOV.
• Hypothesis: PP or HFOV will result in at least 2 additional ventilator-free days (VFD) compared to standard care.

Main Results:

• The primary outcome is ventilator-free days (VFD) through day 28, with nonsurvivors receiving zero VFD.
• Secondary outcomes include nonpulmonary organ failure-free days, 90-day mortality, and post-PICU functional status.
• Adaptive randomization will adjust treatment allocation probabilities based on accumulating trial data.

Conclusions:

• The PROSpect trial aims to generate crucial data to inform clinical decision-making regarding prone positioning and high-frequency oscillatory ventilation in PARDS.
• Findings will support evidence-based respiratory care for critically ill children with PARDS.