Burst Suppression Therapy for Seizures after Cardiac Arrest

(RESTORE Trial)

Overseen By Kevin Bao

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Disqualifiers: Acute cerebral hemorrhage, pregnancy, prisoners

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24-48 hours

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for seizures occurring after a heart attack outside a hospital. Researchers are testing two methods using special brain wave monitoring (EEG) to guide anesthesia: one targets burst suppression (Burst Suppression EEG Target Intravenous Anesthesia), and the other focuses on stopping seizures (Seizure Suppression EEG Target Intravenous Anesthesia). The goal is to determine which method is safer and more practical. Suitable participants have experienced a heart attack outside the hospital, were unconscious upon admission, and have ongoing seizures unresponsive to usual treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a specific brain activity pattern, called burst suppression, is used during anesthesia and is linked to outcomes in patients with severe, ongoing seizures. However, detailed information about its safety remains limited.

Studies suggest that successfully stopping seizures can lead to better patient outcomes, indicating potential safety. Yet, detailed safety information is still lacking.

Both treatments are in Phase 2 trials, indicating sufficient initial safety to progress beyond early testing. However, more information is needed to fully understand their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores innovative ways to manage seizures after cardiac arrest. Traditional treatments often involve anti-seizure medications like benzodiazepines or phenytoin. However, this trial focuses on two novel anesthesia approaches using EEG targets to control brain activity. The Burst Suppression EEG Target approach aims to significantly reduce brain activity, which might protect the brain by minimizing energy consumption. Meanwhile, the Seizure Suppression EEG Target method directly targets seizure activity, potentially offering a more precise control compared to existing treatments. These methods could lead to more effective and tailored seizure management after cardiac arrest.

What evidence suggests that this trial's treatments could be effective for post-cardiac arrest seizures?

Research has shown that burst suppression therapy, which uses anesthesia to create a specific brainwave pattern, links to outcomes in patients with refractory status epilepticus, a severe type of seizure. In this trial, participants in one arm will receive Burst Suppression EEG Target Intravenous Anesthesia. Studies have found that achieving burst suppression can help control seizures. In contrast, participants in another arm will receive Seizure Suppression EEG Target Intravenous Anesthesia, which aims to stop seizures directly using anesthesia. This method has shown good results in some patients. Both treatments in this trial aim to stabilize brain activity after cardiac arrest, offering a potential way to manage seizures in these critical situations. ^{1 2 5 6 7}

Who Is on the Research Team?

Edilberto Amorim, MD

Principal Investigator

Assistant Professor of Neurology

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a non-traumatic, out-of-hospital cardiac arrest and are now in a coma with refractory status epilepticus confirmed by EEG. They must have regained circulation within 45 minutes and be admitted to the ICU. It's not for those with acute brain bleeding or stroke, pregnant women, or prisoners.

Inclusion Criteria

I had a sudden heart stoppage outside of a hospital without injury.

I was diagnosed with a severe seizure condition after a heart attack, confirmed by EEG.

Your heart starts beating again on its own within 45 minutes.

Exclusion Criteria

I have had a recent stroke or brain bleed.

Pregnancy

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive anesthetic treatment targeting burst suppression or seizure suppression on EEG for 24 hours. Intervention may be repeated once in case of PCARSE recurrence.

24-48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment, including seizure recurrence and neurological function at discharge and up to 180 days.

180 days

What Are the Treatments Tested in This Trial?

Interventions

• Burst Suppression EEG Target Intravenous Anesthesia
• Seizure Suppression EEG Target Intravenous Anesthesia

Trial Overview The RESTORE trial is comparing two types of intravenous anesthesia based on EEG targets: one aiming for burst suppression (reducing brain activity) and the other for seizure suppression (stopping seizures), to see which is safer and more feasible after cardiac arrest.

How Is the Trial Designed?

Group I: Seizure Suppression EEG Target Experimental Treatment 1 Intervention

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

Group II: Burst Suppression EEG Target Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

The ZOLL Foundation

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

Burst suppression (BS) is a unique EEG pattern characterized by alternating high-voltage slow waves and low-voltage periods, commonly observed during surgery or in ICU settings.

BS can indicate either increased anesthetic depth or potential cerebral damage, serving as a critical marker for clinicians to assess brain function and therapeutic endpoints in patients with severe neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does electroencephalographic burst suppression still play a role in the perioperative setting? Lobo, FA., Vacas, S., Rossetti, AO., et al.[2022]

Burst-suppression EEG patterns, which show alternating high-power oscillations and periods of inactivity, are observed during conditions like general anesthesia and coma, suggesting they may have protective effects on the brain.

Recent advances in understanding burst-suppression patterns indicate that while they can be used therapeutically, there is ongoing debate about their association with negative clinical outcomes, highlighting the need for careful monitoring and control during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etiology of Burst Suppression EEG Patterns. Shanker, A., Abel, JH., Schamberg, G., et al.[2021]

In a study of 147 adult patients with refractory status epilepticus treated with continuous IV anesthesia, complete burst suppression (≥50% suppression) was achieved in 21% of patients, but this was not linked to better outcomes like seizure termination or survival.

However, in patients with cerebral anoxia, burst suppression was associated with improved outcomes, showing that 72% of those without burst suppression achieved persistent seizure termination compared to only 29% with burst suppression, and survival rates were also higher (50% vs 14%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Induced Burst Suppression and Clinical Outcomes in Patients With Refractory Status Epilepticus: A 9-Year Cohort Study. Fisch, U., Jünger, AL., Baumann, SM., et al.[2023]

Burst suppression is an EEG pattern that can occur due to various conditions, including general anesthesia, and is characterized by alternating high and low amplitude brain activity.

Our study found distinct electrophysiological differences in burst suppression patterns between the anesthetics sevoflurane and propofol, suggesting that they may work through different circuit mechanisms in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol and sevoflurane induce distinct burst suppression patterns in rats. Kenny, JD., Westover, MB., Ching, S., et al.[2020]

Burst-suppression is an electroencephalographic pattern caused by various factors, including metabolic suppression from anesthetic medications, indicating its complex physiological mechanisms.

The review discusses both supporting and opposing evidence for using burst-suppression as a therapeutic measure in perioperative settings, highlighting its potential clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroencephalographic Burst-Suppression, Perioperative Neuroprotection, Postoperative Cognitive Function, and Mortality: A Focused Narrative Review of the Literature. Ma, K., Bebawy, JF.[2023]

In two children undergoing barbiturate anesthesia for severe epilepsy, EEG monitoring revealed epileptiform discharges during periods of burst suppression, highlighting the complexity of interpreting EEG patterns in this context.

The study emphasizes the need to differentiate between true electrocerebral silence and EEG suppression, as well as between epileptiform discharges and burst patterns, to effectively manage anesthesia depth during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epileptic EEG discharges during burst suppression. Jäntti, V., Eriksson, K., Hartikainen, K., et al.[2008]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10186226/

Association Between Induced Burst Suppression and ... In adult patients with RSE treated with IVAD, burst suppression with ≥50% suppression proportion was achieved in every fifth patient and not ...

2. withpower.com withpower.com/trial/phase-2-seizures-4-2023-94a25

Burst Suppression Therapy for Seizures after Cardiac Arrest Research indicates that burst suppression, an EEG pattern used during anesthesia, is associated with outcomes in patients with refractory status epilepticus (a ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05851391

buRst-supprESsion TO Stop Refractory Status Epilepticus ... RESTORE is a randomized clinical trial investigating the safety and feasibility of using EEG treatment targets (burst suppression vs. seizure suppression)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9468095/

EEG monitoring after cardiac arrest - PMC Superimposed rhythmic and periodic EEG patterns (RPPs) that may reflect electrographic seizures have been reported in 10–35% of comatose cardiac ...

5. frontiersin.org frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2021.673529/full

Etiology of Burst Suppression EEG Patterns In this Perspective, we review the origins of burst-suppression patterns and use recent insights to weigh evidence in the controversy.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0300957224002132

EEG for good outcome prediction after cardiac arrest Nearly one-third of comatose patients resuscitated after CA had a non-highly malignant and reactive EEG that was associated with a good long-term outcome.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4836886/

Standardized EEG interpretation accurately predicts prognosis ... To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation.