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

Seizures Clinical Trial

— RESTORE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05851391
• Other study ID #: 21-34336
• Status: Recruiting
• Phase: Phase 2
• Start date: August 7, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: Edilberto Amorim, MD
• Phone: 628-206-3203
• Email: restorestudy[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 30, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anoxic-Ischemic Encephalopathy
• Brain Diseases
• Brain Ischemia
• Heart Arrest
• Hypoxia
• Hypoxia-Ischemia, Brain
• Ischemia
• Refractory Status Epilepticus
• Seizures
• Status Epilepticus

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	The ZOLL Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Seizure recurrence incidence and duration (burden)	Presence of seizures on EEG after initiation of anesthetic maintenance phase	24-48 hours
Secondary	Neurological Function at Discharge (CPC: Cerebral Performance Category)	Cerebral Performance Category score at Discharge	30 days
Secondary	Neurological Function at Discharge (mRS: modified Ranking Scale)	modified Rankin Scale score at Discharge	30 days
Secondary	Neurological Function 90 days (CPC: Cerebral Performance Category)	Cerebral Performance Category score at 90 days	90 days
Secondary	Neurological Function 90 days (mRS: modified Ranking Scale)	modified Rankin Scale score at Discharge	90 days
Secondary	Neurological Function 180 days (mRS: modified Ranking Scale)	modified Rankin Scale score at Discharge	180 days
Secondary	Neurological Function180 days (mRS: modified Ranking Scale)	modified Rankin Scale score at Discharge	180 days
Secondary	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
Secondary	Seizure recurrence incidence and duration (burden)	Presence of seizures on EEG after initiation of anesthetic weaning phase	24-48 hours
Secondary	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