top of page

TTM2 Trial

TTM2 Trial


June 17, 2021

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

Mazen Kherallah

Summarized by: 

What was the research question?

  • In survivors of out-of-hospital cardiac arrest, does targeted hypothermia impact all-cause mortality compared to targeted normothermia?

How did they do it?

  • An open-label trial with blinded assessment of outcomes in 14 countries, 61 institutions.

  • 1861 adults with coma after resuscitation from out-of-hospital cardiac arrest were randomized to undergo targeted hypothermia at 33°C for 28 hours, followed by controlled rewarming at 0.3°C per hour until 40 hours ( 930 patients), or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C) (931patients).

  • The primary outcome was death from any cause at 6 months.

  • Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale.

What did they find?

  • All-cause mortality at 6 months was not significantly different between the hypothermia group and the normothermia group (50% vs, 48%, p = 0.37).

  • Rate of patients with poor functional status (modified Rankin scale 4 to 6) was not significantly different between the hypothermia group and the normothermia group (55% vs. 55%, P=1.09).

  • Hypothermia group had more arrhythmias compared to normothermia group (24% versus 17%, P <0 .001).

Are there any limitations?

  • Results cannot be generalized to in-hospital cardiac arrest.

  • Cooling to a target temperature occurred at a median of 3 hours. Therefore, cannot rule out a benefit effect of earlier.

  • The trial used an absolute risk reduction of 7.5% in mortality based on the Hypothermia After Cardiac arrest trial, this may have been very ambitious and may subject the trial to type II error.

What does it mean?

  • Among survivors of out-of-hospital cardiac arrest, outcomes of targeted hypothermia are not different compared to targeted normothermia in terms of all-cause mortality and neurological functional status at six months.

  • The trial supports the notion that active temperature management and avoidance of hyperthermia are the most the most important factors determining the outcome of survivors of out-of-hospital cardiac arrest rather than hypothermia.


bottom of page