Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation

Study Overview
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Brief Summary
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The COMACARE trial is a pilot multicenter randomized trial to assess the feasibility and effect on brain injury markers of targeting low or high normal arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2) and mean arterial pressure (MAP) in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest. Using factorial design, participants are randomized at admission to intensive care unit to one of eight groups targeting either low or high normal values of PaO2, PaCO2 and MAP for 36 h. In this way, investigators will be assessing the feasibility and effect of all three variables at the same time. The primary outcome is serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. Feasibility outcome is between-group separation in PaO2, PaCO2 and MAP levels. Secondary outcomes include continuous monitoring of cerebral oxygenation, EEG and ECG for 48 h, the levels of NSE, S100B and cardiac troponin at randomization and 24, 48 and 72 h after cardiac arrest and neurological assessment at 6 months after cardiac arrest.

Official Title
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Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation - Targeting High vs. Low Normal Values

Conditions
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Out-of-Hospital Cardiac Arrest

Intervention / Treatment
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* Other: Low normal PaCO2
* Other: High normal PaCO2
* Other: Low normal PaO2
* Other: High normal PaO2
* Other: Low normal MAP
* Other: High normal MAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Witnessed out-of-hospital cardiac arrest with ventricular fibrillation (VF) or ventricular tachycardia (VT) as the initial rhythm Delay of return of spontaneous circulation (ROSC) 10-45 min from the start of the arrest Confirmed or suspected cardiac origin Mechanical ventilation Markedly impaired level of consciousness (no response to verbal commands and Glasgow coma scale [GCS] motor score < 5) Deferred consent possible or likely Active intensive care initiated, including targeted temperature management (33-36 C) Exclusion Criteria: Probable withdrawal of active ICU care due to terminal illness or poor prognosis because of severely reduced functional status before cardiac arrest Confirmed or suspected intracranial pathology and/or suspicion of raised intracranial pressure Pregnancy Severe oxygenation problem (PaO2 / FiO2 < 100 mmHg) Severe COPD

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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Low normal PaCO2, low normal PaO2, low normal MAP | Other: Low normal PaCO2<br>* 4.5-4.7 kPa<br>Other: Low normal PaO2<br>* 10-15 kPa<br>Other: Low normal MAP<br>* 65-75 mmHg<br>|
| Active Comparator: Group 2<br>High normal PaCO2, low normal PaO2, low normal MAP | Other: High normal PaCO2<br>* 5.8-6.0 kPa<br>Other: Low normal PaO2<br>* 10-15 kPa<br>Other: Low normal MAP<br>* 65-75 mmHg<br>|
| Active Comparator: Group 3<br>Low normal PaCO2, high normal PaO2, low normal MAP | Other: Low normal PaCO2<br>* 4.5-4.7 kPa<br>Other: High normal PaO2<br>* 20-25 kPa<br>Other: Low normal MAP<br>* 65-75 mmHg<br>|
| Active Comparator: Group 4<br>High normal PaCO2, high normal PaO2, low normal MAP | Other: High normal PaCO2<br>* 5.8-6.0 kPa<br>Other: High normal PaO2<br>* 20-25 kPa<br>Other: Low normal MAP<br>* 65-75 mmHg<br>|
| Active Comparator: Group 5<br>Low normal PaCO2, low normal PaO2, high normal MAP | Other: Low normal PaCO2<br>* 4.5-4.7 kPa<br>Other: Low normal PaO2<br>* 10-15 kPa<br>Other: High normal MAP<br>* 80-100 mmHg<br>|
| Active Comparator: Group 6<br>High normal PaCO2, low normal PaO2, high normal MAP | Other: High normal PaCO2<br>* 5.8-6.0 kPa<br>Other: Low normal PaO2<br>* 10-15 kPa<br>Other: High normal MAP<br>* 80-100 mmHg<br>|
| Active Comparator: Group 7<br>Low normal PaCO2, high normal PaO2, high normal MAP | Other: Low normal PaCO2<br>* 4.5-4.7 kPa<br>Other: High normal PaO2<br>* 20-25 kPa<br>Other: High normal MAP<br>* 80-100 mmHg<br>|
| Active Comparator: Group 8<br>High normal PaCO2, high normal PaO2, high normal MAP | Other: High normal PaCO2<br>* 5.8-6.0 kPa<br>Other: High normal PaO2<br>* 20-25 kPa<br>Other: High normal MAP<br>* 80-100 mmHg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuron-specific enolase (NSE) serum concentration |  | 48 hour after cardiac arrest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuron-specific enolase (NSE) serum concentration |  | At randomization and 24 and 72 hour after cardiac arrest | 
| S100B protein serum concentration |  | At randomization and 24, 48 and 72 hour after cardiac arrest | 
| Cardiac troponin (TnT) serum concentration |  | At randomization and 24, 48 and 72 hour after cardiac arrest | 
| Cerebral oxygenation monitoring using near infrared spectroscopy (NIRS) monitoring |  | For 48 hour after admission to ICU | 
| Continuous electroencephalography (EEG) monitoring |  | For 48 hour after admission to ICU | 
| Functional status using cerebral performance category (CPC) classification |  | At 30 days and 6 months after cardiac arrest | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Out-of-Hospital Cardiac Arrest, Resuscitation, Hypoxia-Ischemia, Brain