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

Primary Purpose

Hypoxia-Ischemia, Brain, Heart Arrest, Status Epilepticus

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Burst Suppression EEG Target Intravenous Anesthesia
Seizure Suppression EEG Target Intravenous Anesthesia
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoxia-Ischemia, Brain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years old Non-traumatic, out-of-hospital cardiac arrest Comatose on admission - defined as not following commands Return of spontaneous circulation (ROSC) within less than 45 minutes Admission to the intensive care unit Diagnosis of post-cardiac arrest refractory status epilepticus confirmed with continuous EEG monitoring within 7 days from ROSC Exclusion Criteria: Acute cerebral hemorrhage or infarction Pregnancy Prisoners

Sites / Locations

  • Zuckerberg San Francisco General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Burst Suppression EEG Target

Seizure Suppression EEG Target

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

First Posted
February 24, 2023
Last Updated
August 9, 2023
Sponsor
University of California, San Francisco
Collaborators
The ZOLL Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05851391
Brief Title
buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest
Acronym
RESTORE
Official Title
buRst-supprESsion TO Stop Refractory Status Epilepticus Post-cardiac Arrest (RESTORE)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 7, 2023 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
The ZOLL Foundation

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxia-Ischemia, Brain, Heart Arrest, Status Epilepticus, Refractory Status Epilepticus, Seizures, Anoxic-Ischemic Encephalopathy, Anoxia-Ischemia, Cerebral

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Burst Suppression EEG Target
Arm Type
Other
Arm Description
Anesthetic will be titrated to achieve burst suppression on continuous EEG (50-99% attenuation/suppression) for 24 hours.
Arm Title
Seizure Suppression EEG Target
Arm Type
Other
Arm Description
Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours.
Intervention Type
Drug
Intervention Name(s)
Burst Suppression EEG Target Intravenous Anesthesia
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Seizure Suppression EEG Target Intravenous Anesthesia
Intervention Description
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.
Primary Outcome Measure Information:
Title
Post-cardiac arrest refractory status epilepticus control
Description
Continuous EEG will be monitored to determine time to PCARSE recurrence during the anesthetic maintenance and anesthetic weaning phase (combined)
Time Frame
48 hours
Secondary Outcome Measure Information:
Title
Seizure recurrence incidence and duration (burden)
Description
Presence of seizures on EEG after initiation of anesthetic maintenance phase
Time Frame
24-48 hours
Title
Neurological Function at Discharge (CPC: Cerebral Performance Category)
Description
Cerebral Performance Category score at Discharge
Time Frame
30 days
Title
Neurological Function at Discharge (mRS: modified Ranking Scale)
Description
modified Rankin Scale score at Discharge
Time Frame
30 days
Title
Neurological Function 90 days (CPC: Cerebral Performance Category)
Description
Cerebral Performance Category score at 90 days
Time Frame
90 days
Title
Neurological Function 90 days (mRS: modified Ranking Scale)
Description
modified Rankin Scale score at Discharge
Time Frame
90 days
Title
Neurological Function 180 days (mRS: modified Ranking Scale)
Description
modified Rankin Scale score at Discharge
Time Frame
180 days
Title
Neurological Function180 days (mRS: modified Ranking Scale)
Description
modified Rankin Scale score at Discharge
Time Frame
180 days
Title
PCARSE Treatment Intensity
Description
Number of anti-seizure medications and anesthetics used for PCARSE control after initiation of anesthetic maintenance phase and prior to weaning
Time Frame
24-48 hours
Title
Seizure recurrence incidence and duration (burden)
Description
Presence of seizures on EEG after initiation of anesthetic weaning phase
Time Frame
24-48 hours
Title
PCARSE Treatment Intensity
Description
Dose of anti-seizure medications and anesthetics used for PCARSE control after initiation of anesthetic maintenance phase and prior to weaning
Time Frame
24-48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years old Non-traumatic, out-of-hospital cardiac arrest Comatose on admission - defined as not following commands Return of spontaneous circulation (ROSC) within less than 45 minutes Admission to the intensive care unit Diagnosis of post-cardiac arrest refractory status epilepticus confirmed with continuous EEG monitoring within 7 days from ROSC Exclusion Criteria: Acute cerebral hemorrhage or infarction Pregnancy Prisoners
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Edilberto Amorim, MD
Phone
628-206-3203
Email
restorestudy@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Dominica Randazzo
Phone
(415)514-2120
Email
restorestudy@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edilberto Amorim, MD
Organizational Affiliation
Assistant Professor of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zuckerberg San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edilberto Amorim, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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