Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial

Paul J Young; Carol L Hodgson; Diane Mackle; Anne M Mather; Richard Beasley; Rinaldo Bellomo; Stephen Bernard; Kathy Brickell; Adam M Deane; Glenn Eastwood; Simon Finfer; Alisa M Higgins; Anna Hunt; Cassie Lawrence; Natalie J Linke; Edward Litton; Christine F McDonald; James Moore; Alistair D Nichol; Shaanti Olatunji; Rachael L Parke; Sandra Peake; Paul Secombe; Ian M Seppelt; Anne Turner; Tony Trapani; Andrew Udy; Jessica Kasza; LOGICAL management committee, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Irish Critical Care Trials Group

doi:10.1016/j.ccrj.2023.06.007

Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial

Crit Care Resusc. 2023 Jul 26;25(3):140-146. doi: 10.1016/j.ccrj.2023.06.007. eCollection 2023 Sep.

Authors

Paul J Young^{1

2

3

4}, Carol L Hodgson^{3

4}, Diane Mackle², Anne M Mather³, Richard Beasley², Rinaldo Bellomo^{3

4

5

6

7}, Stephen Bernard^{8

9}, Kathy Brickell¹⁰, Adam M Deane^{4

5}, Glenn Eastwood^{3

6}, Simon Finfer^{11

12}, Alisa M Higgins³, Anna Hunt², Cassie Lawrence², Natalie J Linke³, Edward Litton^{13

14}, Christine F McDonald^{15

16

17}, James Moore^{1

2}, Alistair D Nichol^{3

8

18}, Shaanti Olatunji², Rachael L Parke^{2

3

19

20}, Sandra Peake^{2

21

22}, Paul Secombe²³, Ian M Seppelt^{3

11

24}, Anne Turner², Tony Trapani³, Andrew Udy^{3

8}, Jessica Kasza²⁵; LOGICAL management committee, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Irish Critical Care 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 Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁶ Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia.
⁷ Data Analytics Research and Evaluation Centre, Austin Hospital, Melbourne, Victoria, Australia.
⁸ Department of Intensive Care & Hyperbaric Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
⁹ Department of Intensive Care, Victorian Heart Hospital, Melbourne, Victoria, Australia.
¹⁰ University College Dublin Clinical Research Centre at St Vincents University Hospital, Dublin, Ireland.
¹¹ The George Institute for Global Health, University of New South Wales, Sydney, Australia.
¹² Faculty of Medicine, University College London, London, United Kingdom.
¹³ School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
¹⁴ Intensive Care Unit, Fiona Stanley Hospital, Robin Warren Drive, Murdoch, Western Australia, Australia.
¹⁵ Department of Respiratory and Sleep Medicine, Austin Health, Melbourne, Victoria, Australia.
¹⁶ Faculty of Medicine, University of Melbourne, Victoria, Australia.
¹⁷ Institute for Breathing and Sleep, Melbourne, Victoria, Australia.
¹⁸ University College Dublin Clinical Research Centre at St Vincent's University Hospital, Dublin, Ireland.
¹⁹ Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand.
²⁰ School of Nursing, The University of Auckland, Auckland, New Zealand.
²¹ Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
²² Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
²³ Intensive Care Unit, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.
²⁴ Intensive Care Unit, Nepean Hospital, Sydney, New South Wales, Australia.
²⁵ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Abstract

Background: The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial.

Objective: The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial.

Design setting and participants: LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX).

Main outcome measures: The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind).

Conclusions: The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias.

Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).

Keywords: Cardiac arrest; Hyperoxia; Hypoxia; Hypoxic ischaemic encephalopathy; Oxygen therapy.