Target Temperature Management (TTM) after cardiac arrest trial 2
Research type
Research Study
Full title
Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest. A Randomised Clinical Trial
IRAS ID
228332
Contact name
Matt Wise
Contact email
Sponsor organisation
Region Skåne, Skånevård Sund
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 3 months, 29 days
Research summary
Research Summary
Around 300,000 Europeans suffer an out-of-hospital cardiac arrest (OHCA) each year. Around 20% achieve return of spontaneous circulation (ROSC) and are usually unconscious requiring admission to intensive care where ~50% are discharged alive. Many interventions have been investigated to lower mortality and improve neurologic function but to date induced hypothermia is the only intervention that has shown promising results in preliminary clinical trials. The Target Temperature Management after OHCA 2 (TTM2) trial is a continuation of the collaboration that resulted in the previous Target Temperature Management after OHCA (TTM1).\nThe TTM1 trial (NCT01020916) was a multicentre, multinational, outcome assessor-blinded, parallel group, randomised clinical trial comparing two strict target temperature regimens of 33°C and 36°C in adult patients, who had sustained ROSC and were unconscious after OHCA, when admitted to hospital. The trial did not demonstrate any difference in survival or neurologic function at six months after the arrest. \nThis planned trial is an international, multicentre, parallel group, randomised, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared to normothermia with early treatment of fever (>37.8°C), as the latter is associated with worse outcomes. Patients eligible for inclusion will be unconscious adult patients with OHCA of a presumed cardiac cause with stable ROSC. The intervention period will commence at the time of randomisation. Rapid cooling in the hypothermia group will be achieved by means of cold fluids and state-of-the-art cooling devices. In the normothermia arm the aim will be early treatment of fever (>37.8°C) when needed. All participants will be sedated, mechanically ventilated throughout the intervention period of 40 hours. Participants remaining unconscious will be assessed according to European Resuscitation Council’s recommendations for neurological prognostication after cardiac arrest. Follow-up will be performed at 30 days, 6 and 24 months after cardiac arrest.\n
Summary of Results
The trial ran across multiple hospitals in Europe, Australia and the USA. The study was managed by the Sponsors in Sweden and funded via a grant from the Swedish Research Council.
The study ran from 2018 to 2021 and recruited 1900 participants
The study aimed to build upon a previous study about the effects and safety of cooling patients who had suffered a cardiac arrest outside of the hospital environment.
This study compared two temperature management strategies in adults who experienced an out of hospital cardiac arrest. Patients received either targeted hypothermia (cooling the body to 33°C) followed by controlled rewarming or targeted normothermia (maintaining body temperature at 37.8°C).
All patients who had suffered an out of hospital cardiac arrest and needed treatment in the critical care department, and, who were eligible for the trial were recruited as soon as possible after they were admitted to hospital.
The main questions the study aimed to answer were how many patients survived to 6 months after enrolment as well as their quality of life.
During the trial 50% of patients were cooled using devices commonly used within critical care departments to a body temperature of 33 degrees Celsius for 28 hours, then slowly warmed to a normal temperature. The other 50% of patient were only cooled if their temperature was over 37.8 degrees Celsius, which is considered a fever. During this time all other interventions and care were given as normal.
Of those patients who survived, a follow up session was conducted at 6 months post cardiac arrest. This assessed how well patients had recovered and how they rated their quality of life
The study found that patients who received cooling to 33 degrees were more likely to suffer from an arrhythmia - an abnormal heart rhythm, which is common in patients admitted to critical care
The study found no significant difference in survival at 6 months between the hypothermia group and the normothermia group. Both groups had similar rates of death, indicating that hypothermia did not lead to a lower rate of death compared to normothermia. The assessments at 6 months were also similar between the 2 groups
This study has suggested that there is little benefit of cooling patients after an out of hospital cardiac arrest and this needs to be looked in to further.
Plans are currently in progress to begin a follow-on study looking further at temperature management strategies, as well as sedation and blood pressure targets in patients who have suffered an out of hospital cardiac arrest You can learn more about this study via the
You can learn more about this study via the website TTM2 | Improving evidence based care in cardiac arrest (http://scanmail.trustwave.com/?c=261&d=49CN5cPi2k84w1XdgBCQi3IR-LPSCcyO66akJPfJqQ&u=http%3a%2f%2fttm2trial%2eorg)
REC name
Wales REC 3
REC reference
17/WA/0191
Date of REC Opinion
15 Sep 2017
REC opinion
Further Information Favourable Opinion