A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial

PurposeTo obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).MethodsWe designed a multicentre pilot trial with 1:1:1 randomization to either 32 degrees C (n=52), 33 degrees C (n=49) or 34 degrees C (n=49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of3, blindly assessed at 90days.ResultsAt baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 degrees C (13.5%), 33 degrees C (34.7%) and 34 degrees C (28.6%; p=0.03). The percentage of patients with an mRS3 at 90days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 degrees C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 degrees C, respectively (trend test p=0.04). All levels of cooling were well tolerated.ConclusionsThere were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 degrees C.Clinical trial registrationClinicalTrials.gov unique identifier: NCT02035839 (http://clinicaltrials.gov).