Sedation, Temperature and Pressure After Cardiac Arrest and Resuscitation

Study Overview
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Brief Summary
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The STEPCARE-trial is a 2x2x2 randomised trial studying patients who have been resuscitated from cardiac arrest and who are comatose. It will include three different interventions focusing on sedation targets, temperature targets and mean arterial pressure targets.

Detailed Description
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3500 patients who are comatose after cardiac arrest will be included in a trial studying three separate targets. All patients will be randomised to a control or an intervention arm for sedation, temperature and blood pressure targets. These are. Continuous deep sedation for 36 hours or minimal sedation (SEDCARE) Fever management with or without a feedback-controlled device (TEMPCARE) A mean arterial pressure target of >85mmHg or >65mmHg. (MAPCARE) Participants will be followed up at 30 days and 6 months. The primary outcome will be survival at 6 months.

Official Title
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Sedation, Temperature and Pressure After Cardiac Arrest and Resuscitation

Conditions
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Cardiac Arrest With Successful Resuscitation, Hypoxia, Brain

Intervention / Treatment
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* Device: Feedback-controlled temperature device
* Other: High MAP
* Other: Deep sedation
* Other: Fever control without a device
* Other: Low MAP
* Other: Minimal sedation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Out-of-hospital cardiac arrest Sustained ROSC - defined as 20 minutes with signs of circulation without the need for chest compressions Unconsciousness defined as not being able to obey verbal commands (FOUR-score motor response of <4) or being intubated and sedated because of agitation after sustained ROSC. Eligible for intensive care without restrictions or limitations Inclusion within 4 hours of ROSC Exclusion Criteria: On ECMO prior to randomization Pregnancy Suspected or confirmed intracranial hemorrhage Previously randomized in the STEPCARE trial.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: 2x2x2 factorial, with all patients taking part in each factor.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sedation, temperature device and high MAP<br>Continuous deep sedation for 36 hours Fever management with a feedback-controlled device if temperature above 37.7°C. A mean arterial pressure target of >85mmHg. | Device: Feedback-controlled temperature device<br>* If core body temperature exceeds 37.7°C a feedback controlled-device will be used and set at 37.5°C.<br>Other: High MAP<br>* A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Deep sedation<br>* Deep sedation for at least 36h<br>|
| Active Comparator: Sedation, no temperature device and high MAP<br>Continuous deep sedation for 36 hours. Fever management without a feedback-controlled device. A mean arterial pressure target of >85mmHg. | Other: High MAP<br>* A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Deep sedation<br>* Deep sedation for at least 36h<br>Other: Fever control without a device<br>* Management of fever in the ICU without a device<br>|
| Active Comparator: Sedation, temperature device and low MAP<br>Continuous deep sedation for 36 hours. Fever management with a feedback-controlled device if temperature above 37.7°C. A mean arterial pressure target of >65mmHg. | Device: Feedback-controlled temperature device<br>* If core body temperature exceeds 37.7°C a feedback controlled-device will be used and set at 37.5°C.<br>Other: Deep sedation<br>* Deep sedation for at least 36h<br>Other: Low MAP<br>* A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>|
| Active Comparator: Sedation, no temperature device and low MAP<br>Continuous deep sedation for 36 hours. Fever management without a feedback-controlled device. A mean arterial pressure target of >65mmHg. | Other: Deep sedation<br>* Deep sedation for at least 36h<br>Other: Fever control without a device<br>* Management of fever in the ICU without a device<br>Other: Low MAP<br>* A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>|
| Active Comparator: Minimal sedation, temperature device and high MAP<br>Minimal sedation (and early extubation if possible). Fever management with a feedback-controlled device if temperature above 37.7°C. A mean arterial pressure target of >85mmHg. | Device: Feedback-controlled temperature device<br>* If core body temperature exceeds 37.7°C a feedback controlled-device will be used and set at 37.5°C.<br>Other: High MAP<br>* A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Minimal sedation<br>* A strategy of minimal sedation in the ICU, used only as needed to facilitate transport, imaging and invasive procedures.<br>|
| Active Comparator: Minimal sedation, no temperature device and high MAP<br>Minimal sedation (and early extubation if possible). Fever management without a feedback-controlled device. A mean arterial pressure target of >65mmHg. | Other: High MAP<br>* A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Fever control without a device<br>* Management of fever in the ICU without a device<br>Other: Minimal sedation<br>* A strategy of minimal sedation in the ICU, used only as needed to facilitate transport, imaging and invasive procedures.<br>|
| Active Comparator: Minimal sedation, temperature device and low MAP<br>Minimal sedation (and early extubation if possible). Fever management with a feedback-controlled device if temperature above 37.7°C. A mean arterial pressure target of >65mmHg. | Device: Feedback-controlled temperature device<br>* If core body temperature exceeds 37.7°C a feedback controlled-device will be used and set at 37.5°C.<br>Other: Low MAP<br>* A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Minimal sedation<br>* A strategy of minimal sedation in the ICU, used only as needed to facilitate transport, imaging and invasive procedures.<br>|
| Active Comparator: Minimal sedation, no temperature device and low MAP<br>Minimal sedation (and early extubation if possible). Fever management without a feedback-controlled device. A mean arterial pressure target of >65mmHg. | Other: Fever control without a device<br>* Management of fever in the ICU without a device<br>Other: Low MAP<br>* A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h.<br>Other: Minimal sedation<br>* A strategy of minimal sedation in the ICU, used only as needed to facilitate transport, imaging and invasive procedures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Landmark mortality at follow-up performed at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional outcome | Proportion of patients who have a mRS score of 4-6 | 6 months | 
| Health-related quality of life | EQ5D-5L VAS | 6 months |