buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest

Study Overview
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Brief Summary
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RESTORE is a randomized clinical trial investigating the safety and feasibility of using EEG treatment targets (burst suppression vs. seizure suppression) for post-cardiac arrest refractory status epilepticus treatment.

Detailed Description
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Rationale: Seizures emerge as a complication of hypoxic-ischemic brain injury in near a third of patients successfully resuscitated from cardiac arrest. Seizures post-cardiac arrest can be refractory to treatment with anti-seizure medications and anesthetics may be used for refractory status epilepticus control. Anesthetic treatment guided by continuous EEG can target burst suppression or seizure suppression, however it is not known which strategy is superior for achieving PCARSE control. Objective: determine the safety and feasibility of post-cardiac arrest refractory status epilepticus (PCARSE) treatment using EEG goals for intravenous anesthetic titration (burst suppression vs. seizure suppression). Clinical Trial Phase: II Study Design: prospective, randomized, open-label, blinded end-point, concurrently-controlled, parallel arms design clinical trial. Study Period: two years Study Population: unconscious cardiac arrest survivors with return of spontaneous circulation who develop post-cardiac arrest refractory status epilepticus (PCARSE). Interventions: anesthetic use targeting burst suppression vs. seizure suppression on EEG for 24 hours. Intervention maybe repeated using the dame EEG target once in case of PCARSE recurrence. Sample Size: 30 subjects randomized in a 1:1 ratio to either burst suppression or seizure suppression EEG targets. Primary Endpoints: Safety and feasibility of seizure control using burst suppression or seizure suppression EEG targets for PCARSE treatment. Secondary Endpoints: Seizure recurrence incidence, time to seizure recurrence, number and dose of anti-seizure medication and anesthetic needed for PCARSE control, Death or disability according to the Cerebral Performance Category at Discharge (30 days), and Death or disability according to the modified Rankin Scale at Discharge (30 days). Risks: Participants receiving anesthetics for PCARSE treatment will be monitored for hypotension, propofol infusion syndrome, and hypertriglyceridemia. Patients with PCARSE are at high risk for death and prolonged hospital stays.

Official Title
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buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest (RESTORE)

Conditions
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Hypoxia-Ischemia, Brain, Heart Arrest, Status Epilepticus, Refractory Status Epilepticus, Seizures, Anoxic-Ischemic Encephalopathy, Anoxia-Ischemia, Cerebral

Intervention / Treatment
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* Drug: Burst Suppression EEG Target Intravenous Anesthesia
* Drug: Seizure Suppression EEG Target Intravenous Anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Non-traumatic, out-of-hospital cardiac arrest Comatose on admission - defined as not following commands Return of spontaneous circulation (ROSC) within less than 45 minutes Admission to the intensive care unit Diagnosis of post-cardiac arrest refractory status epilepticus confirmed with continuous EEG monitoring within 7 days from ROSC Exclusion Criteria: Acute cerebral hemorrhage or infarction Pregnancy Prisoners

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Burst Suppression EEG Target<br>Anesthetic will be titrated to achieve burst suppression on continuous EEG (50-99% attenuation/suppression) for 24 hours. | Drug: Burst Suppression EEG Target Intravenous Anesthesia<br>* The objective of the burst suppression EEG target is to stop seizures by titrating the anesthetic infusion to suppress most of the EEG background (>50% suppressed/attenuated). After this 24-hour period, this target would be continued for 24 hours. The anesthetic will then be tapered under EEG monitoring. In case of PCARSE recurrence, the intervention with the same target will be re-initiated for another cycle of 24 hours.<br>|
| Other: Seizure Suppression EEG Target<br>Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours. | Drug: Seizure Suppression EEG Target Intravenous Anesthesia<br>* is to stop seizures by titrating the anesthetic infusion without suppressing most of the EEG background. This target would be continued for 24 hours. After this 24-hours period, this target would be continued for 24 hours. The anesthetic will then be tapered under EEG monitoring. In case of PCARSE recurrence, the intervention with the same target will be re-initiated for another cycle of 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-cardiac arrest refractory status epilepticus control | Continuous EEG will be monitored to determine time to PCARSE recurrence during the anesthetic maintenance and anesthetic weaning phase (combined) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure recurrence incidence and duration (burden) | Presence of seizures on EEG after initiation of anesthetic maintenance phase | 24-48 hours | 
| Neurological Function at Discharge (CPC: Cerebral Performance Category) | Cerebral Performance Category score at Discharge | 30 days | 
| Neurological Function at Discharge (mRS: modified Ranking Scale) | modified Rankin Scale score at Discharge | 30 days | 
| Neurological Function 90 days (CPC: Cerebral Performance Category) | Cerebral Performance Category score at 90 days | 90 days | 
| Neurological Function 90 days (mRS: modified Ranking Scale) | modified Rankin Scale score at Discharge | 90 days | 
| Neurological Function 180 days (mRS: modified Ranking Scale) | modified Rankin Scale score at Discharge | 180 days | 
| Neurological Function180 days (mRS: modified Ranking Scale) | modified Rankin Scale score at Discharge | 180 days | 
| PCARSE Treatment Intensity | Number of anti-seizure medications and anesthetics used for PCARSE control after initiation of anesthetic maintenance phase and prior to weaning | 24-48 hours | 
| Seizure recurrence incidence and duration (burden) | Presence of seizures on EEG after initiation of anesthetic weaning phase | 24-48 hours | 
| PCARSE Treatment Intensity | Dose of anti-seizure medications and anesthetics used for PCARSE control after initiation of anesthetic maintenance phase and prior to weaning | 24-48 hours |