Clinical trial NCT06401707: PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest
Official title: PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Arrest
Seizures
Status Epilepticus
Keywords: heart arrest
seizure
status epilepticus
prophylaxis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2024-05-07
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Brain injury is the main cause of death and disability for patients surviving cardiac arrest resuscitation and seizures are diagnosed in up to a third of these patients. The investigators are proposing a pilot randomized placebo-controlled clinical trial to evaluate the safety and feasibility of perampanel use for post-cardiac arrest status epilepticus (PCARSE) prevention after cardiac arrest.

Detailed description: More than 500,000 Americans have a cardiac arrest every year and 100,000 survive to hospital admission. Brain injury is the main cause of death and disability for patients surviving cardiac arrest resuscitation and seizures are diagnosed in up to a third of these patients. Seizures with or without muscle jerks, i.e. myoclonic seizures, are the most common seizure type after a cardiac arrest. Despite being common, seizures are usually refractory to treatment (post-cardiac arrest refractory status epilepticus) and the vast majority of patients with this diagnosis die. We are proposing a pilot randomized placebo-controlled clinical trial to evaluate the safety and feasibility of perampanel use for PCARSE prevention after cardiac arrest. Perampanel is a non-competitive AMPA glutamate receptor antagonist approved for adjunctive treatment of partial-onset seizures and primary generalized tonic-clonic seizures, however there are no randomized trials in critically ill cardiac arrest patients at risk for seizures. This medication has been used for the management of refractory status epilepticus, including status epilepticus post-cardiac arrest. We will randomize patients to placebo or perampanel after admission to the intensive care unit. The study's primary outcome will be the incidence of severe adverse events. Secondary efficacy and safety endpoints include incidence of seizures and PCARSE, seizure frequency, time to seizure control, number of anti-seizure medications necessary for seizure control, duration of treatment with anesthetics for seizure control, and time to coma awakening. This study will help determine the safety and feasibility of primary seizure prophylaxis after cardiac arrest.

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 from the time of cardiac arrest (defined as the time of 911 or EMS (emergency medical services) witnessed arrest)
* Admission to the intensive care unit at Zuckerberg San Francisco General Hospital

Exclusion Criteria:

* Acute cerebral hemorrhage or infarction
* Pregnancy
* Prisoner
* Severe kidney function impairment with creatinine clearance inferior to 30 ml/min
* Severe liver impairment with liver function tests five times above the upper limit of normal
* Electrographic or electroclinical seizures diagnosis using American Clinical Neurophysiology criteria confirmed by an epileptologist after cardiac arrest

Primary outcomes:
measure: Safety and tolerability of perampanel
timeFrame: 7 days
measure: Adverse and Serious Adverse Events
timeFrame: 7 days
Secondary outcomes:
measure: Incidence of post-cardiac arrest refractory status epilepticus
timeFrame: 7 days
measure: Incidence of post-cardiac arrest seizures
timeFrame: 7 days
measure: Treatment intensity of post-cardiac arrest refractory status epilepticus
timeFrame: 7 days
measure: Time to start of post-cardiac arrest refractory status epilepticus
timeFrame: 7 days
measure: Neurological function at 180 days
timeFrame: 180 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Edilberto Amorim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beretta S, Padovano G, Stabile A, Coppo A, Bogliun G, Avalli L, Ferrarese C. Efficacy and safety of perampanel oral loading in postanoxic super-refractory status epilepticus: A pilot study. Epilepsia. 2018 Oct;59 Suppl 2:243-248. doi: 10.1111/epi.14492. Epub 2018 Aug 29.
citation: Hirsch LJ, Fong MWK, Leitinger M, LaRoche SM, Beniczky S, Abend NS, Lee JW, Wusthoff CJ, Hahn CD, Westover MB, Gerard EE, Herman ST, Haider HA, Osman G, Rodriguez-Ruiz A, Maciel CB, Gilmore EJ, Fernandez A, Rosenthal ES, Claassen J, Husain AM, Yoo JY, So EL, Kaplan PW, Nuwer MR, van Putten M, Sutter R, Drislane FW, Trinka E, Gaspard N. American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2021 Version. J Clin Neurophysiol. 2021 Jan 1;38(1):1-29. doi: 10.1097/WNP.0000000000000806. No abstract available.