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. 2023 Oct 19;24(2):137-149.
doi: 10.51893/2022.2.OA4. eCollection 2022 Jun 6.

Protocol and statistical analysis plan for the mega randomised registry trial research program comparing conservative versus liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX)

Paul J Young  1   2   3   4 , Yaseen M Arabi  5   6 , Sean M Bagshaw  7 , Rinaldo Bellomo  3   4   8   9 , Tomoko Fujii  3   10   11 , Rashan Haniffa  12   13   14 , Carol L Hodgson  3   4   15   16 , Bharath Kumar Tirupakuzhi Vijayaraghavan  17   18 , Edward Litton  19   20 , Diane Mackle  2 , Alistair D Nichol  3   15   21   22 , Jessica Kasza  23 ; Mega-ROX Management Committee; Australian and New Zealand Intensive Care Society Clinical Trials Group; Crit Care Asia and Africa Network; Irish Critical Care Clinical Trials Group; Alberta Health Services Critical Care Strategic Clinical Network
Affiliations

Protocol and statistical analysis plan for the mega randomised registry trial research program comparing conservative versus liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX)

Paul J Young et al. Crit Care Resusc. .

Abstract

Background: The effect of conservative versus liberal oxygen therapy on 90-day in-hospital mortality in patients who require unplanned invasive mechanical ventilation in an intensive care unit (ICU) is uncertain and will be evaluated in the mega randomised registry trial research program (Mega-ROX). Objective: To summarise the protocol and statistical analysis plan for Mega-ROX. Design, setting and participants: Mega-ROX is a 40 000-patient parallel-group, registry-embedded clinical trial in which adults who require unplanned invasive mechanical ventilation in an ICU will be randomly assigned to conservative or liberal oxygen therapy. Within this overarching trial research program, three nested parallel randomised controlled trials will be conducted. These will include patients with suspected hypoxic ischaemic encephalopathy (HIE) following resuscitation from a cardiac arrest, patients with sepsis, and patients with non-HIE acute brain injuries or conditions. Main outcome measures: The primary outcome is in-hospital allcause 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 proportion of patients discharged home. Results and conclusions: Mega-ROX will compare the effect of conservative versus liberal oxygen therapy on 90-day in-hospital mortality in critically ill adults who receive unplanned invasive mechanical ventilation in an ICU. The protocol and a pre-specified approach to analyses are reported here to mitigate analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12620000391976).

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Conflict of interest statement

All authors declare that they do not have any potential conflict of interest in relation to this manuscript.

Figures

Figure 1
Figure 1
Overview of Mega-ROX HIE = hypoxic ischaemic encephalopathy. Mega-ROX = mega randomised registry trial research program comparing conservative versus liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU. RCT = randomised controlled trial.
Figure 2
Figure 2
Management of patients assigned to conservative oxygen therapy and those assigned to liberal oxygen therapy Fio2 = fraction of inspired oxygen. Mega-ROX = mega randomised registry trial research program comparing conservative versus liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU. Pao2 = arterial partial pressure of oxygen. Sao2 = arterial oxygen saturation. Spo2 = arterial oxygen saturation measured by peripheral pulse oximetry.
Figure 3
Figure 3
Data recorded via the study website and then used to identify patients in registry databases ICU = intensive care unit.
See this image and copyright information in PMC

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