TAME Cardiac Arrest Trial
Research type
Research Study
Full title
Targeted therapeutic mild hypercapnia after resuscitated cardiac arrest: A phase III multi-centre randomised controlled trial
IRAS ID
227541
Contact name
Matt Wise
Contact email
Sponsor organisation
Australian and New Zealand Intensive Care Research Centre (ANZIC-RC)
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
Australian New Zealand Clinical Trials Registry, ACTRN12617000036314p
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Research Summary
Cardiac arrest is a common and catastrophic event with substantial human and financial costs. It is well established that cardiac arrest leads to brain injury. However, what is not widely appreciated is that, after circulation has been restored, cerebral (brain) hypoperfusion (inadequate blood supply) continues. Ongoing cerebral vasoconstriction (blood vessel constriction) and cerebral hypoxia (inadequate oxygen) has been demonstrated using imaging and metabolic technologies including positron emission tomography, ultrasound, jugular bulb oxygen saturation and cerebral oximetry.\n\nA likely mechanism responsible for sustained early cerebral hypoperfusion relates to impaired cerebrovascular auto-regulation which is the ability of the brain to maintain its’ own perfusion. Impaired cerebral auto-regulation may make even a normal arterial carbon dioxide tension (PaCO2) (the major physiological regulator of cerebral blood flow) insufficient to achieve and maintain adequate cerebral perfusion and, consequently, cerebral oxygenation. PaCO2 is the major determinant of cerebral blood flow and an increased PaCO2 (hypercapnia) markedly increases cerebral blood flow. Arterial carbon dioxide is modifiable and, as such, is a potential therapeutic target. \n\nThe TAME Cardiac Arrest Trial is a phase III multi-centre randomised controlled trial in resuscitated cardiac arrest patients. This trial will determine whether targeted therapeutic mild hypercapnia (TTMH) applied during the first 24 hours of mechanical ventilation in the intensive care unit improves neurological outcome at 6 months compared to standard care (targeted normocapnia (TN).\n\nSupported by compelling preliminary data, significant improvements in patient outcomes are achievable with this simple and cost-free therapy. Recruiting 1,700 patients, for multiple sites in many countries, this will be one of the largest trial ever conducted involving resuscitated cardiac arrest patients admitted to ICU. If the TAME Cardiac Arrest Trial confirms that TTMH is effective, its findings will improve the lives of many patients, transform clinical practice and yield major economic gains worldwide.
Summary of Results
The leading cause of death and poor recovery among patients who have been resuscitated following out-of-hospital cardiac arrest (OOHCA) is lack of oxygen delivery and blood flow to the brain.
Lack of oxygen to the brain after cardiac arrest worsens brain damage and contributes to poor patient recovery and survival.
Intensive Care Unit (ICU) patients who receive slightly higher arterial carbon dioxide (CO2) after a cardiac arrest applied during mechanical breathing support, may have improved brain recovery.
The TAME Study aimed to find out if hypercapnia (a slightly raised carbon dioxide level) improved patients mental functioning and recovery 6 months after their cardiac arrest.
The trial was run in 63 ICUs across 17 countries, ran from 2018 to 2022 and recruited 1700 patients. The study was funded by the National Health and Medical Research Council of Australia.
All patients who had suffered an out of hospital cardiac arrest and were eligible for the trial were recruited as soon as possible after they were admitted to hospital.
50% of patient recruited were allocated to a slightly higher CO2 target and the other 50% were allocated to a 'normal' CO2 target. Both groups received this intervention for 24 hours.
Those patients who survived were followed up at 6 months and were asked how well they had recovered and how they rated their quality of life.
The results showed that maintaining slightly higher CO2 did not improve brain recovery at six months compared to current practice. There was no difference in ICU patient recovery or survival.
The TAME findings support the current approach to CO2 management during intensive care stay after an out of hospital cardiac arrest.
More research is needed to minimise practice variability and optimise ventilation management to improve patients outcomes following an out of hospital cardiac arrest.REC name
Wales REC 3
REC reference
17/WA/0192
Date of REC Opinion
29 Sep 2017
REC opinion
Further Information Favourable Opinion