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

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).