Clinical trial NCT05851391: buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest
Official title: buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest (RESTORE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypoxia-Ischemia, Brain
Heart Arrest
Status Epilepticus
Refractory Status Epilepticus
Seizures
Anoxic-Ischemic Encephalopathy
Anoxia-Ischemia, Cerebral
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: The ZOLL Foundation
First posted: 2023-05-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Post-cardiac arrest refractory status epilepticus control
timeFrame: 48 hours
Secondary outcomes:
measure: Seizure recurrence incidence and duration (burden)
timeFrame: 24-48 hours
measure: Neurological Function at Discharge (CPC: Cerebral Performance Category)
timeFrame: 30 days
measure: Neurological Function at Discharge (mRS: modified Ranking Scale)
timeFrame: 30 days
measure: Neurological Function 90 days (CPC: Cerebral Performance Category)
timeFrame: 90 days
measure: Neurological Function 90 days (mRS: modified Ranking Scale)
timeFrame: 90 days
measure: Neurological Function 180 days (mRS: modified Ranking Scale)
timeFrame: 180 days
measure: Neurological Function180 days (mRS: modified Ranking Scale)
timeFrame: 180 days
measure: PCARSE Treatment Intensity
timeFrame: 24-48 hours
measure: Seizure recurrence incidence and duration (burden)
timeFrame: 24-48 hours
measure: PCARSE Treatment Intensity
timeFrame: 24-48 hours
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: Assistant Professor of Neurology
name: Edilberto Amorim, MD
role: PRINCIPAL_INVESTIGATOR
References: