Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis)

Abstract

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain.

Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial.

Design setting and participants: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial.

Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home.

Results and conclusions: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.

Keywords: Critical care; Hyperoxaemia; Hypoxaemia; Intensive care; Oxygen therapy; Sepsis.