Early Cessation of Sedation and TTM in Patients With a Favourable EEG After Cardiac Arrest

Study Overview
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Brief Summary
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The objective of this study is to estimate the feasibility and safety of early weaning from ICU treatment in patients after cardiac arrest and an early (< 12 h) favourable EEG pattern (indicating no or mild postanoxic encephalopathy).

Detailed Description
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Comatose patients after cardiac arrest are treated on intensive care units with sedative medication, targeted temperature management (TTM), mechanical ventilation, and hemodynamic support. Despite substantial variation in the severity of the encephalopathy and even lack of unequivocal evidence of efficacy of sedation and TTM, all patients receive standard treatment. The severity of the postanoxic encephalopathy can reliably be assessed with the electroencephalogram (EEG). A continuous EEG pattern within the first 12 hours after cardiac arrest (favorable EEG) is strongly associated with a good neurological outcome and reflects a very mild or transient encephalopathy. The investigators hypothesize that this subgroup of patients, with a favorable EEG will not benefit from prolonged sedation and TTM. The objective of this study is to estimate the feasibility and safety of early weaning from ICU treatment in patients after cardiac arrest and an early (< 12 h) favourable EEG pattern. The study design is a cluster randomized crossover design with two treatment arms. The intervention contrast will be early cessation of sedation and TTM, with subsequent weaning from mechanical ventilation if appropriate (intervention group) vs. standard care, including sedation and TTM for at least 24-48 hours (control group). The investigators will include forty adult patients admitted to the ICU with postanoxic encephalopathy after cardiac arrest and an early (<12 hours) favorable EEG pattern.

Official Title
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Early Cessation of Sedation and TTM in Patients With a Favourable EEG After Cardiac Arrest: a Feasibility and Safety Study

Conditions
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Hypoxia-Ischemia, Brain, Heart Arrest

Intervention / Treatment
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* Other: Early cessation of sedation and TTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients after cardiac arrest admitted to the ICU for treatment with sedation, TTM and mechanical ventilation. Age 18 years or older. Continuous EEG measurement started within 12 hours after cardiac arrest. Favourable EEG pattern within 12 hours after arrest, defined as a continuous background pattern (NVN, 2019; Ruijter et al., 2019). Possibility to stop sedative treatment within three hours after identification of a favourable EEG pattern. Written informed consent (deferred). Exclusion Criteria: A known history of another medical condition with limited life expectancy (<6 months). Any progressive brain illness, such as a brain tumour or neurodegenerative disease. Pre-admission Glasgow Outcome Scale Extended score of 4 or lower. Reason other than neurological condition to continue sedation and/or ventilation. Follow-up impossible due to logistic reasons.

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A cluster randomized crossover design with two treatment arms (early cessation from sedation and TTM vs standard care).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early cessation of sedation and TTM<br>Early cessation of sedation and targeted temperature management (TTM), with subsequent weaning from mechanical ventilation if appropriate (intervention group). | Other: Early cessation of sedation and TTM<br>* Early cessation of sedation and TTM, with subsequent weaning from mechanical ventilation if appropriate<br>|
| No Intervention: Standard Care<br>Standard care, including sedation and targeted temperature management (TTM) for at least 24-48 hours (control group). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation time in hours |  | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of ICU stay |  | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 
| Total sedation time |  | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 
| Need for re-intubation |  | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 
| Need for restarting sedation |  | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 
| Number of serious adverse events (SAEs) |  | at 3 and 6 months | 
| Mortality |  | at 30 days, 3 months and 6 months | 
| Complications during intensive care admission | Number of pneumonia, sepsis (according to sepsis 3 criteria), bleeding (any cause), cardiac arrhythmia (any associated with hemodynamic compromise), new cardiac arrest and thrombopenia | During the complete ICU admission (from admission to the ICU until discharge from the ICU, up to 30 days). | 
| Neurological outcome measured at the Extended Glasgow Outcome Scale (GOSE) | The CPC ranges from 1 to 8, with higher scores meaning better neurological outcome. | at 3 and 6 months | 
| Neurological outcome measured at the Cerebral Performance Category (CPC) | The CPC ranges from 1 to 5, with higher scores meaning worse neurological outcome. | at 3 and 6 months | 
| Cognitive functioning | Montreal Cognitive Assessment (MOCA) score via videoconference. The MOCA ranges from 0 to 30, with higher scores meaning better cognitive functioning. | at 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EEG, targeted temperature management (TTM)