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)

Paul J Young^{1

2

3

4}, Abdulrahman Al-Fares^{5

6}, Diptesh Aryal⁷, Yaseen M Arabi⁸, Muhammad Sheharyar Ashraf⁹, Sean M Bagshaw¹⁰, Abigail Beane^{11

12}, Airton L de Oliveira Manoel¹³, Layoni Dullawe¹², Fathima Fazla¹², Tomoko Fujii^{3

14

15}, Rashan Haniffa^{11

12

16

17}, Carol L Hodgson^{3

4

18

19}, Anna Hunt², Bharath Kumar Tirupakuzhi Vijayaraghavan^{20

21}, Giovanni Landoni^{22

23}, Cassie Lawrence², Israel Silva Maia²⁴, Diane Mackle², Mohd Zulfakar Mazlan^{25

26}, Alistair D Nichol^{3

18

27

28}, Shaanti Olatunji², Aasiyah Rashan^{12

29}, Sumayyah Rashan^{12

30}, Jessica Kasza³¹; Mega-ROX management committee; Australian and New Zealand Intensive Care Society Clinical Trials Group; Critical Care Asia and Africa Network; Irish Critical Care-Clinical Trials Group

Affiliations

¹ Intensive Care Unit, Wellington Hospital, Wellington, New Zealand.
² Medical Research Institute of New Zealand, Wellington, New Zealand.
³ Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
⁴ Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Department of Anesthesia, Critical Care Medicine, and Pain Medicine, Al-Amiri Hospital, Ministry of Health, Kuwait.
⁶ Kuwait Extracorporeal Life Support Program, Al-Amiri Center for Respiratory and Cardiac Failure, Ministry of Health, Kuwait.
⁷ Nepal Intensive Care Research Foundation, Kathmandu, Nepal.
⁸ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, and Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
⁹ Department of Anesthesia and Critical Care Unit, Lady Reading Hospital, Peshawar, Pakistan.
¹⁰ Department of Critical Care Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada.
¹¹ Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
¹² National Intensive Care Surveillance - MORU (NICS-MORU), Colombo, Sri Lanka.
¹³ Department of Critical Care Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman.
¹⁴ Intensive Care Unit, Jikei University Hospital, Tokyo, Japan.
¹⁵ Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
¹⁶ Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹⁷ University College Hospital, London, United Kingdom.
¹⁸ The Intensive Care Unit, Alfred Health, Melbourne, Victoria, Australia.
¹⁹ The George Institute for Global Health, Sydney, New South Wales, Australia.
²⁰ Department of Critical Care Medicine, Apollo Hospitals, Chennai, India.
²¹ The George Institute for Global Health, New Delhi, India.
²² Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²³ Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
²⁴ HCor Research Institute, São Paulo, Brazil.
²⁵ Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
²⁶ Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia.
²⁷ School of Medicine and Medical Sciences, University College Dublin, Ireland.
²⁸ Department of Anaesthesia and Intensive Care, St Vincent's Hospital, Dublin, Ireland.
²⁹ University College London, Institute of Health Informatics, London, United Kingdom.
³⁰ Division of Surgery and Interventional Science, University College London, London, United Kingdom.
³¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

PMID: 37876605
PMCID: PMC10581255
DOI: 10.1016/j.ccrj.2023.04.008

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)

Paul J Young et al. Crit Care Resusc. 2023.

. 2023 May 22;25(2):106-112.

doi: 10.1016/j.ccrj.2023.04.008. eCollection 2023 Jun.

Authors

Affiliations

¹ Intensive Care Unit, Wellington Hospital, Wellington, New Zealand.
² Medical Research Institute of New Zealand, Wellington, New Zealand.
³ Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
⁴ Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Department of Anesthesia, Critical Care Medicine, and Pain Medicine, Al-Amiri Hospital, Ministry of Health, Kuwait.
⁶ Kuwait Extracorporeal Life Support Program, Al-Amiri Center for Respiratory and Cardiac Failure, Ministry of Health, Kuwait.
⁷ Nepal Intensive Care Research Foundation, Kathmandu, Nepal.
⁸ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, and Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
⁹ Department of Anesthesia and Critical Care Unit, Lady Reading Hospital, Peshawar, Pakistan.
¹⁰ Department of Critical Care Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada.
¹¹ Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
¹² National Intensive Care Surveillance - MORU (NICS-MORU), Colombo, Sri Lanka.
¹³ Department of Critical Care Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman.
¹⁴ Intensive Care Unit, Jikei University Hospital, Tokyo, Japan.
¹⁵ Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
¹⁶ Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹⁷ University College Hospital, London, United Kingdom.
¹⁸ The Intensive Care Unit, Alfred Health, Melbourne, Victoria, Australia.
¹⁹ The George Institute for Global Health, Sydney, New South Wales, Australia.
²⁰ Department of Critical Care Medicine, Apollo Hospitals, Chennai, India.
²¹ The George Institute for Global Health, New Delhi, India.
²² Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²³ Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
²⁴ HCor Research Institute, São Paulo, Brazil.
²⁵ Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
²⁶ Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia.
²⁷ School of Medicine and Medical Sciences, University College Dublin, Ireland.
²⁸ Department of Anaesthesia and Intensive Care, St Vincent's Hospital, Dublin, Ireland.
²⁹ University College London, Institute of Health Informatics, London, United Kingdom.
³⁰ Division of Surgery and Interventional Science, University College London, London, United Kingdom.
³¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

PMID: 37876605
PMCID: PMC10581255
DOI: 10.1016/j.ccrj.2023.04.008

Erratum in

Erratum for previously published articles.
[No authors listed] [No authors listed] Crit Care Resusc. 2023 Oct 12;25(3):158. doi: 10.1016/j.ccrj.2023.09.001. eCollection 2023 Sep. Crit Care Resusc. 2023. PMID: 39726436 Free PMC article.

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.

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Figures

**Fig. 1**
Overview of steps undertaken by the data monitoring committee at interim analyses Abbreviations: Mega-ROX: Mega randomised registry trial comparing two approaches to oxygen therapy in the intensive care unit.

See this image and copyright information in PMC

References

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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)

Affiliations

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)

Authors

Affiliations

Erratum in

Abstract

Figures

References

LinkOut - more resources

Full Text Sources