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

Study Overview
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Brief Summary
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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.

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

Conditions
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Out-Of-Hospital Cardiac Arrest

Intervention / Treatment
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* Device: Target Temperature Management of 34°C
* Device: Target Temperature Management of 32°C
* Device: Target Temperature Management of 33°C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent (obtained from their legal representative) 18 years of age or older and less than 80 years old. Witnessed OHCA of presumed cardiac cause Sustained ROSC (when chest compressions have not been required for 20 consecutive minutes and signs of circulation persist) Initial shockable cardiac rhythm (documented by ECG or AED) Interval from collapse to advance life support < 20 minutes Interval from collapse to ROSC < 60 minutes Lack of meaningful response to verbal commands upon arrival to hospital after suffering non-traumatic cardiac arrest in an out-of-hospital setting Systolic blood pressure of >90 maintained for a least 30 minutes post-ROSC without pressors, or with a stable dose of pressors Exclusion Criteria: Traumatic cardiac arrest Toxicological etiology Known or suspected pregnancy Do Not Attempt to Resuscitate order in force Unwitnessed arrest In-Hospital arrest Anatomy, previous surgery or disease state contraindicating femoral venous access Received neuromuscular blocking agents prior to assessing level of consciousness following ROSC Neurological evaluation insufficient/incomplete after ROSC but prior to randomization. Body core temperature < 34ºC at randomization Current Inferior Vena Cava (IVC) filter Known history of acute neurological illness or severe functional disabilities prior to arrest (e.g., seizures, traumatic brain injury, increased intracranial pressures, intra-cerebral hemorrhage, etc). Known hypersensitivity to hypothermia including a history of Raynaud's disease Suspected or confirmed acute intracranial bleeding Suspected or confirmed acute stroke Terminal illness or life expectancy of less than 3 months prior to arrest Currently enrolled in another investigational new drug or device trial that has not completed the primary endpoint or that clinically interferes with this Trial's endpoints (For the purpose of this protocol, subjects involved in extended follow-up trials or registries for products that are currently commercially available are not considered enrolled in an investigational trial). Transferred from a non-participating hospital.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Target Temperature Management of 34°C<br>In hospital target temperature management to achieve core body temperature of 34°C for 24 hours. | Device: Target Temperature Management of 34°C<br>* In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.<br>|
| Other: Target Temperature Management of 32°C<br>In hospital target temperature management to achieve core body temperature of 32°C for 24 hours. | Device: Target Temperature Management of 32°C<br>* In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.<br>|
| Other: Target Temperature Management of 33°C<br>In hospital target temperature management to achieve core body temperature of 33°C for 24 hours. | Device: Target Temperature Management of 33°C<br>* In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest. |  | at 90 days after out-of-hospital cardiac arrest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | 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 |  | 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 |  | 26 hours | 
| Treatment Success: 4. rate of cooling in °C per hour |  | Per hour | 
| Treatment Success: 5. rate of rewarming in °C per hour |  | Per hour | 
| Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion |  | 90 days | 
| Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve) |  | 90 days | 
| Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion |  | 90 days | 
| Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve) |  | 90 days | 
| Outcomes: 5. Survival at 90 days measured as proportion |  | 90 days | 
| Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve) |  | 90 days | 
| Outcomes: 7. ICU-free survival within 90 days measured in days |  | 90 days | 
| Outcomes: 8. Hospital-free survival within 90 days measured in days |  | 90 days | 
| Outcomes: 9. Adverse events a. Device related b. Procedure related |  | 90 days | 
| Subgroup analysis | 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. | 1 year | 
| Subgroups of Special Interest Age of Patients | 18 to 65 years; or (ii) > 65 years. | Duration of the trial | 
| Timings of initiation of hypothermia | (ii) > 65 years. | <4 hours of restoration of spontaneous circulation; or > 4 hours | 
| Patient Gender | Subgroups to assess Consistency of Effect | Male or Female | 
| Observational status of arrest |  | Witnessed by EMS; Witnessed by bystanders | 
| Location of cardiac arrest |  | Public;Home; or Group residence (e.g. nursing home) | 
| Bystander CPR status: |  | Performed; or Not performed. | 
| AED status: |  | Applied by layperson;Applied by EMS provider;Not applied | 
| Response time interval from call to initiation of CPR by EMS, among witnessed arrests: |  | < 10 minutes;> 10 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Target Temperature Management, Cooling comatose survivors from OHCA, Good neurological outcome at modified Rankin Score (mRS) ≤ 3