About The Study
The TTM2 trial is a continuation of the collaboration that resulted in the previous Target Temperature Management after out-of-hospital cardiac arrest trial (hereafter: TTM1). With its planned size TTM2 will supersede the TTM1 trial as the largest trial on temperature management as a post-cardiac arrest intervention.
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 return of spontaneous circulation and were unconscious after out-of-hospital cardiac arrest, when admitted to hospital. The trial did not demonstrate any difference in survival until end of trial (Hazard Ratio with a point estimate in favour of 36°C of 1.06 (95% confidence interval 0.89-1.28; P=0.51)) or neurologic function at six months after the arrest, measured with the Cerebral Performance Category (CPC) and the modified Rankin Scale (mRS).
This planned trial is a international, multicentre, parallel group, non-commercial, 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)
Patients eligible for inclusion will be unconscious adult patients with out-of-hospital cardiac arrest of a presumed cardiac cause with stable return of spontaneous circulation. Randomisation will be performed by a physician in the emergency department, in the angiography suite or in the intensive care unit via web-based application using permuted blocks with varying sizes, stratified by site. Due to the nature of the intervention, health care staff will not be blinded to the intervention. However, the health care personnel who will assess outcomes will be blinded to temperature allocation, as will those who perform prognostication.
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 (intravascular/body-surface/nasal/oesophageal). A closed loop system will be used to maintain the target temperature. In the normothermia arm the aim will be early treatment of fever (≥37.8°C) using pharmacological measures and physical cooling when needed. For participants who develop a temperature of 37.8°C (trigger), a device will be used and set at 37.5°C. All participants will be sedated, mechanically ventilated and haemodynamically supported throughout the intervention period of 40 hours. After 28 hours the participants in the hypothermia group will be rewarmed during 12 hours.
Participants who remain unconscious will be assessed according to a conservative protocol based on the European Resuscitation Council (ERC)’s recommendations for neurological prognostication after cardiac arrest.