TY - JOUR
T1 - Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains)
AU - Young, Paul J.
AU - Al-Fares, Abdulrahman
AU - Aryal, Diptesh
AU - Arabi, Yaseen M.
AU - Ashraf, Muhammad Sheharyar
AU - Bagshaw, Sean M.
AU - Mat-Nor, Mohd Basri
AU - Beane, Abigail
AU - Borghi, Giovanni
AU - de Oliveira Manoel, Airton L.
AU - Dullawe, Layoni
AU - Fazla, Fathima
AU - Fujii, Tomoko
AU - Haniffa, Rashan
AU - Hodgson, Carol L.
AU - Hunt, Anna
AU - Lawrence, Cassie
AU - Mackle, Diane
AU - Mangal, Kishore
AU - Nichol, Alistair D.
AU - Olatunji, Shaanti
AU - Rashan, Aasiyah
AU - Rashan, Sumayyah
AU - Tomazini, Bruno
AU - Kasza, Jessica
AU - for the Mega-ROX management committee, the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Brazilian Research in Intensive Care Network, the Critical Care Asia and Africa Network, the Irish Critical Care-Clinical Trials Group
N1 - Funding Information:
Mega-ROX Brains is funded by grants from the Health Research Council of New Zealand and by an unrestricted donation from the Alpha Charitable Trust. In Canada, Mega-ROX has received funding from the Pragmatic Trials Platform – Alberta Strategy for Patient-Oriented Research Support Unit. The funding bodies have had no input into the design or conduct of the trial or into the statistical analysis plan and will have no input into analysis or reporting of the results. The study is coordinated in New Zealand by the Medical Research Institute of New Zealand and in Australia by the Australian and New Zealand Intensive Care Research Centre. The study is coordinated in Brazil by the HCor Research Institute. The study is coordinated in Ireland by the Irish Critical Care Clinical Trials Network, which is supported by the Health Research Board. The study is coordinated in Canada by the University of Alberta. The study is coordinated in Japan by Jikei University. The study is coordinated in Asia by the Critical Care Asia Network and in Africa by the Critical Care Africa Network (parts of the National Intensive Care Surveillance, Mahidol–Oxford Tropical Medicine Research Unit [NICS-MORU] collaboration), which are supported by a Wellcome Innovations grant ( 215522 ). This study is endorsed by the Australia and New Zealand Intensive Care Society Clinical Trials Group, the Irish Critical Care Clinical Trials Group, and the Alberta Health Services Critical Care Strategic Clinical Network. This study is approved by the Japanese Intensive Care Research Group.
Funding Information:
Mega-ROX Brains is funded by grants from the Health Research Council of New Zealand and by an unrestricted donation from the Alpha Charitable Trust. In Canada, Mega-ROX has received funding from the Pragmatic Trials Platform – Alberta Strategy for Patient-Oriented Research Support Unit. The funding bodies have had no input into the design or conduct of the trial or into the statistical analysis plan and will have no input into analysis or reporting of the results. The study is coordinated in New Zealand by the Medical Research Institute of New Zealand and in Australia by the Australian and New Zealand Intensive Care Research Centre. The study is coordinated in Brazil by the HCor Research Institute. The study is coordinated in Ireland by the Irish Critical Care Clinical Trials Network, which is supported by the Health Research Board. The study is coordinated in Canada by the University of Alberta. The study is coordinated in Japan by Jikei University. The study is coordinated in Asia by the Critical Care Asia Network and in Africa by the Critical Care Africa Network (parts of the National Intensive Care Surveillance, Mahidol–Oxford Tropical Medicine Research Unit [NICS-MORU] collaboration), which are supported by a Wellcome Innovations grant (215522). This study is endorsed by the Australia and New Zealand Intensive Care Society Clinical Trials Group, the Irish Critical Care Clinical Trials Group, and the Alberta Health Services Critical Care Strategic Clinical Network. This study is approved by the Japanese Intensive Care Research Group.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/3
Y1 - 2023/3
N2 - Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving 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 Brains trial. Design, setting, and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d 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 participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).
AB - Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving 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 Brains trial. Design, setting, and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d 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 participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).
KW - Critical care
KW - Hyperoxaemia
KW - Hypoxaemia
KW - Intensive care
KW - Oxygen
KW - Oxygen therapy
KW - Stroke
KW - Subarachnoid haemorrhage
KW - Traumatic brain injury
UR - https://www.scopus.com/pages/publications/85163395532
U2 - 10.1016/j.ccrj.2023.04.011
DO - 10.1016/j.ccrj.2023.04.011
M3 - Article
C2 - 37876994
AN - SCOPUS:85163395532
SN - 1441-2772
VL - 25
SP - 53
EP - 59
JO - Critical Care and Resuscitation
JF - Critical Care and Resuscitation
IS - 1
ER -