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

Abstract

Objectives: Respiratory management for pediatric acute respiratory distress syndrome (PARDS) remains largely supportive without data to support one approach over another, including supine versus prone positioning (PP) and conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFOV).

Design: We present the research methodology of a global, multicenter, two-by-two factorial, response-adaptive, randomized controlled trial of supine versus PP and CMV versus HFOV in high moderate-severe PARDS, the Prone and Oscillation Pediatric Clinical Trial ( PROSpect , www.ClinicalTrials.gov , NCT03896763).

Setting: Approximately 60 PICUs with on-site extracorporeal membrane oxygenation support in North and South America, Europe, Asia, and Oceania with experience using PP and HFOV in the care of patients with PARDS.

Patients: Eligible pediatric patients (2 wk old or older and younger than 21 yr) are randomized within 48 h of meeting eligibility criteria occurring within 96 h of endotracheal intubation.

Interventions: One of four arms, including supine/CMV, prone/CMV, supine/HFOV, or prone/HFOV. We hypothesize that children with high moderate-severe PARDS treated with PP or HFOV will demonstrate greater than or equal to 2 additional ventilator-free days (VFD).

Measurements and main results: The primary outcome is VFD through day 28; nonsurvivors receive zero VFD. Secondary and exploratory outcomes include nonpulmonary organ failure-free days, interaction effects of PP with HFOV on VFD, 90-day in-hospital mortality, and among survivors, duration of mechanical ventilation, PICU and hospital length of stay, and post-PICU functional status and health-related quality of life. Up to 600 patients will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur 28 days after 300 patients are randomized and every 100 patients thereafter. At these randomization updates, new allocation probabilities will be computed based on intention-to-treat trial results, increasing allocation to well-performing arms and decreasing allocation to poorly performing arms. Data will be analyzed per intention-to-treat for the primary analyses and per-protocol for primary, secondary, and exploratory analyses.

Conclusions: PROSpect will provide clinicians with data to inform the practice of PP and HFOV in PARDS.