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

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Seizure Suppression EEG Target Intravenous Anesthesia; Drug: Burst Suppression EEG Target Intravenous Anesthesia

Study type: Interventional

Funder types: Other

Identifiers

NCT05851391

21-34336

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

30 participants in 2 patient groups

Burst Suppression EEG Target

Other group

Description:

Anesthetic will be titrated to achieve burst suppression on continuous EEG (50-99% attenuation/suppression) for 24 hours.

Treatment:

Drug: Burst Suppression EEG Target Intravenous Anesthesia

Seizure Suppression EEG Target

Other group

Description:

Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours.

Treatment:

Drug: Seizure Suppression EEG Target Intravenous Anesthesia