Anoxia-Ischemia, Cerebral, Anoxic-Ischemic Encephalopathy, Heart Arrest, Hypoxia-Ischemia, Brain, Refractory Status Epilepticus, Seizures, Status Epilepticus
Conditions
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.
Interventions
DRUGBurst 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.
DRUGSeizure 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.
Sponsors
University of California, San Francisco
The ZOLL Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-cardiac arrest refractory status epilepticus control | 48 hours | Continuous EEG will be monitored to determine time to PCARSE recurrence during the anesthetic maintenance and anesthetic weaning phase (combined) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure recurrence incidence and duration (burden) | 24-48 hours | Presence of seizures on EEG after initiation of anesthetic maintenance phase |
| Neurological Function at Discharge (CPC: Cerebral Performance Category) | 30 days | Cerebral Performance Category score at Discharge |
| Neurological Function at Discharge (mRS: modified Ranking Scale) | 30 days | modified Rankin Scale score at Discharge |
| Neurological Function 90 days (CPC: Cerebral Performance Category) | 90 days | Cerebral Performance Category score at 90 days |
| Neurological Function 90 days (mRS: modified Ranking Scale) | 90 days | modified Rankin Scale score at Discharge |
| Neurological Function 180 days (mRS: modified Ranking Scale) | 180 days | modified Rankin Scale score at Discharge |
| Neurological Function180 days (mRS: modified Ranking Scale) | 180 days | modified Rankin Scale score at Discharge |
| PCARSE Treatment Intensity | 24-48 hours | Number of anti-seizure medications and anesthetics used for PCARSE control after initiation of anesthetic maintenance phase and prior to weaning |
Countries
United States
Contacts
CONTACTEdilberto Amorim, MD
CONTACTKevin Bao
PRINCIPAL_INVESTIGATOREdilberto Amorim, MD
Assistant Professor of Neurology
Outcome results
None listed