BRIEF SYNOPSIS

Protocol Title

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients

Acronym

ICECAP

Clinical Trial Phase

Phase II/III

Study Design

Randomized, response-adaptive, duration/dose finding, comparative effectiveness clinical trial with blinded outcome assessment

Sites / Period

22 NETT Hubs + ROC and Ancillary Sites (~50 hospitals) / 4 years

Study Population

Comatose adult survivors of out of hospital cardiac arrest that have already been rapidly cooled using a definitive temperature control method.  Those with and without initial shockable rhythms will be studied as distinct populations.  

Primary Study Objectives

To characterize the duration response curve for hypothermia and determine in each of two populations:

A. the shortest duration of cooling that provides the maximal treatment effect, and

B. whether the  duration-response implies efficacy versus no cooling

Secondary Study Objectives

i.        to characterize safety of varying durations of cooling,

ii.        to characterize the effect on neuropsychological outcomes,

iii.        to characterize the effect on patient reported quality of life.

Sample Size

Maximum of 1800 subjects

Inclusion Criteria

Coma after resuscitation from out of hospital cardiac arrest, >18 years of age, <34 deg C within 240 minutes, definitive temperature control device applied, Informed consent from LAR including intent to maintain life support for 96 hours, enrollment within 6 hours of initiation of cooling

Exclusion Criteria

Hemodynamic instability, pre-existing condition confounding outcome determination, pre-existing terminal illness, unlikely to survive to outcome determination, planned early withdrawal of life support, presumed sepsis as etiology of arrest, prisoner

Study Intervention

The intervention will be random allocation to duration of cooling after cardiac arrest.

Primary Outcome

Modified Rankin scale (mRS) at 90 days after return of spontaneous circulation.  

Statistical Analysis for Primary Outcome

Modeling of duration response using a mean weighted mRS incorporating both the proportion of subjects achieving a good neurological outcome and degree of impairment among those with good neurological outcomes.  Identification of the shortest duration of cooling that provides the maximum treatment effect.  Determination of superiority of any longer duration compared to any shorter duration.