Protocol summary and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial

Alistair Nichol; Rinaldo Bellomo; Bridget Ady; Niklas Nielsen; Carol Hodgson; Rachael Parke; Shay McGuinness; Markus Skrifvars; Dion Stub; Stephen Bernard; Fabio Taccone; John Archer; Ary Serpa Neto; Tony Trapani; Kate Ainscough; Anna Hunt; Jim Kutsogiannis; Glenn M Eastwood

doi:10.51893/2021.4.OA2

Protocol summary and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial

Crit Care Resusc. 2023 Oct 18;23(4):374-385. doi: 10.51893/2021.4.OA2. eCollection 2021 Dec 6.

Authors

Alistair Nichol^{1

2

3}, Rinaldo Bellomo^{2

4}, Bridget Ady², Niklas Nielsen⁵, Carol Hodgson², Rachael Parke⁶, Shay McGuinness⁶, Markus Skrifvars⁷, Dion Stub^{8

9}, Stephen Bernard⁸, Fabio Taccone^{10

11}, John Archer¹², Ary Serpa Neto², Tony Trapani², Kate Ainscough¹, Anna Hunt¹³, Jim Kutsogiannis¹⁴, Glenn M Eastwood^{2

4}

Affiliations

¹ University College Dublin-Clinical Research Centre, St Vincent's University Hospital, Dublin, Ireland.
² Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
³ Intensive Care Unit, Alfred Hospital, Melbourne, VIC, Australia.
⁴ Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.
⁵ Department of Clinical Sciences Lund, Anesthesiology and Intensive Care, Helsingborg Hospital, Lund University, Lund, Sweden.
⁶ Cardiothoracic and Vascular Intensive Care and High Dependency Unit, Auckland, City Hospital, Auckland, New Zealand.
⁷ HUS Emergency Medicine and Services, Department of Diagnostics and Therapeutics, University of Helsinki, Helsinki, Finland.
⁸ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁹ Cardiology Departments at Alfred Heath and Western Health, Melbourne, VIC, Australia.
¹⁰ Department of Intensive Care, Hôpital Erasme, Belgium.
¹¹ Université Libre de Bruxelles (ULB) Brussels, Belgium.
¹² Division of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
¹³ Medical Research Institute of New Zealand, Wellington, New Zealand.
¹⁴ Critical Care Medicine, Neurocritical Care, Royal Alexandra Hospital, Edmonton, Alberta, Canada.

Abstract

Background: Targeted therapeutic mild hypercapnia may attenuate brain injury in comatose adults resuscitated from out-of-hospital cardiac arrest. Objective: To describe the study protocol and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial. Design, setting, participants and interventions: TAME is a phase 3, multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial that will be conducted in intensive care units in Australia, Canada, Ireland, Saudi Arabia, New Zealand, Scandinavia, Singapore, Central and Western Europe, and the United Kingdom. A total of 1700 comatose adults resuscitated from out-of-hospital cardiac arrest will be randomly assigned to 24 hours of targeted therapeutic mild hypercapnia (arterial carbon dioxide tension 50-55 mmHg) or targeted normocapnia (arterial carbon dioxide tension 35-45 mmHg) in a 1:1 ratio. TAME recruitment began in March 2018 and is expected to be complete in September 2021. Main outcome measures: The primary outcome measure is the proportion of participants with a favourable functional outcome at 6 months. Functional outcomes will be assessed using the Glasgow Outcome Scale-Extended (GOSE); this scale ranges from 1 to 8, with a higher value indicating a better outcome. We will define participants with a GOSE of 5 to 8 as having a favourable functional outcome. Secondary outcomes include 6-month mortality, cognitive function and quality of life. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: TAME will compare the effect of targeted therapeutic mild hypercapnia versus targeted normocapnia on functional outcomes in adults resuscitated from out-of-hospital cardiac arrest who are admitted to an intensive care unit. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12617000036314p) and ClinicalTrials.gov (NCT03114033).

Associated data

ClinicalTrials.gov/NCT03114033