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). The 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 6 months after the arrest. This 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.
The objective of this trial will be to assess the beneficial and harmful effects of post-ischaemic hypothermia when compared with normothermia and early treatment of fever in unconscious adults after out-of-hospital cardiac arrest.
Dr Niklas Nielsen