PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest

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.

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