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

Phase 2

Recruiting

• Conditions: Heart Arrest; Refractory Status Epilepticus; Hypoxia-Ischemia, Brain; Seizures; Anoxia-Ischemia, Cerebral; Anoxic-Ischemic Encephalopathy; Status Epilepticus
• Interventions: Drug: Burst Suppression EEG Target Intravenous Anesthesia; Drug: Seizure Suppression EEG Target Intravenous Anesthesia

• Registration Number: NCT05851391
• Lead Sponsor: University of California, San Francisco

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-02-24
• Study First Submitted QC: 2023-05-01
• Study First Posted: 2023-05-09
• Study Start: 2023-08-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2026-11-30
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Age ≥18 years old
2. Non-traumatic, out-of-hospital cardiac arrest
3. Comatose on admission - defined as not following commands
4. Return of spontaneous circulation (ROSC) within less than 45 minutes
5. Admission to the intensive care unit
6. Diagnosis of post-cardiac arrest refractory status epilepticus confirmed with continuous

EEG monitoring within 7 days from ROSC

Exclusion Criteria

1. Acute cerebral hemorrhage or infarction
2. Pregnancy
3. Prisoners

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Burst Suppression EEG Target	Burst Suppression EEG Target Intravenous Anesthesia	Anesthetic will be titrated to achieve burst suppression on continuous EEG (50-99% attenuation/suppression) for 24 hours.
Seizure Suppression EEG Target	Seizure Suppression EEG Target Intravenous Anesthesia	Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Zuckerberg San Francisco General Hospital; 🇺🇸 San Francisco, California, United States