Clinical Trial: Finding the Optimal Cooling tempeRature After Out-of-HoSpiTal Cardiac Arrest

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of Out-of-hospital Cardiac Arrest.

Brief Summary: To assess the fraction of subjects surviving with good neurological outcome at 90 days for 3 different levels of hypothermia, in comatose survivors from out-of-hospital cardiac arrest.

Detailed Summary:
Sponsor: ZOLL Circulation, Inc., USA

Current Primary Outcome: Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest. [ Time Frame: at 90 days after out-of-hospital cardiac arrest ]

Original Primary Outcome: Good neurological status (modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest. [ Time Frame: at 90 days after out-of-hospital cardiac arrest ]

Current Secondary Outcome:

• Treatment Success: 1. proportion of subjects that can be therapeutically cooled to randomly allocated target temperature ±0.3°C (as measured by the temperature probe) [ Time Frame: 24 hours ]
• Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia [ Time Frame: 24 hours ]
• Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia [ Time Frame: 26 hours ]
• Treatment Success: 4. rate of cooling in °C per hour [ Time Frame: Per hour ]
• Treatment Success: 5. rate of rewarming in °C per hour [ Time Frame: Per hour ]
• Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion [ Time Frame: 90 days ]
• Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve) [ Time Frame: 90 days ]
• Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion [ Time Frame: 90 days ]
• Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve) [ Time Frame: 90 days ]
• Outcomes: 5. Survival at 90 days measured as proportion [ Time Frame: 90 days ]
• Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve) [ Time Frame: 90 days ]
• Outcomes: 7. ICU-free survival within 90 days measured in days [ Time Frame: 90 days ]
• Outcomes: 8. Hospital-free survival within 90 days measured in days [ Time Frame: 90 days ]
• Outcomes: 9. Adverse events a. Device related b. Procedure related [ Time Frame: 90 days ]
• Subgroup analysis [ Time Frame: 1 year ]
  A priori plan to assess heterogeneity of effect among specific subgroups of special interest as well as to assess the consistency of treatment effect among different subpopulations defined by each of multiple baseline characteristics of the patients. These will be assessed by repeating the primary analysis in the subgroups defined below, using interaction terms.
• Subgroups of Special Interest Age of Patients [ Time Frame: Duration of the trial ]
  18 to 65 years; or (ii) > 65 years.
• Timings of initiation of hypothermia [ Time Frame: <4 hours of restoration of spontaneous circulation; or > 4 hours ]
  (ii) > 65 years.
• Patient Gender [ Time Frame: Male or Female ]
  Subgroups to assess Consistency of Effect
• Observational status of arrest [ Time Frame: Witnessed by EMS; Witnessed by bystanders ]
• Location of cardiac arrest [ Time Frame: Public;Home; or Group residence (e.g. nursing home) ]
• Bystander CPR status: [ Time Frame: Performed; or Not performed. ]
• AED status: [ Time Frame: Applied by layperson;Applied by EMS provider;Not applied ]
• Response time interval from call to initiation of CPR by EMS, among witnessed arrests: [ Time Frame: < 10 minutes;> 10 minutes. ]

Original Secondary Outcome:

• Good neurological status (mRS ≤ 3) at discharge after out-of-hospital cardiac arrest [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 7 days after out-of-hospital cardiac arrest ]
• Good neurological status (mRS ≤ 3) at one year after out-of-hospital cardiac arrest [ Time Frame: at one year after out-of-hospital cardiac arrest ]
• Evaluate covariates of the primary outcome at discharge, 90 days and one year. [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 7 days, 90 days and one year ]
• To assess safety with each target temperature with regard to infection, cardiac arrhythmia, electrolyte disorders and bleeding at 72 h and 7 days. [ Time Frame: at 72 hours and 7 days ]

Dates:
Date Received: November 27, 2013
Date Started: March 2014
Date Completion:
Last Updated: June 9, 2016
Last Verified: June 2016