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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Edilberto Amorim, MD; Phone Number: 628-206-3203; Email: restorestudy@ucsf.edu
• Study Contact Backup: Name: Dominica Randazzo; Phone Number: (415)514-2120; Email: restorestudy@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Recruiting
      • Zuckerberg San Francisco General Hospital
      • Contact: Edilberto Amorim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Burst Suppression EEG Target; 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; 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.
Other: Seizure Suppression EEG Target; Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours.	Drug: Seizure Suppression EEG Target Intravenous Anesthesia; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: The ZOLL Foundation
• Investigators: Principal Investigator: Edilberto Amorim, MD, Assistant Professor of Neurology

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Seizures; Brain Diseases; Heart Arrest; Hypoxia; Hypoxia-Ischemia, Brain; Status Epilepticus; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 21-34336

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes