PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest

Seizures Clinical Trial

— PROSPER  

Official title:

PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06401707
• Other study ID #: 23-39712
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2024
• Est. completion date: October 20, 2026

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: Edilberto Amorim, MD
• Phone: 628-206-3203
• Email: prosperstudy[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: October 20, 2026
• Est. primary completion date: May 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Arrest
• Seizures
• Status Epilepticus

Intervention

Drug:
• Perampanel
Perampanel is a non-competitive AMPA glutamate receptor antagonist.
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of perampanel	percentage of participants who are able to complete the 5-day course of perampanel or placebo.	7 days
Primary	Adverse and Serious Adverse Events	percentage of participants with treatment-related adverse and serious adverse events in perampanel or placebo arms.	7 days
Secondary	Incidence of post-cardiac arrest refractory status epilepticus	percentage of participants with post-cardiac arrest refractory status epilepticus in perampanel or placebo arms.	7 days
Secondary	Incidence of post-cardiac arrest seizures	percentage of participants with post-cardiac arrest seizures in perampanel or placebo arms.	7 days
Secondary	Treatment intensity of post-cardiac arrest refractory status epilepticus	number of anti-seizure medications and anesthetics needed for post-cardiac arrest status epilepticus control in perampanel or placebo arms.	7 days
Secondary	Time to start of post-cardiac arrest refractory status epilepticus	percentage of participants with post-cardiac arrest refractory status epilepticus in perampanel or placebo arms.	7 days
Secondary	Neurological function at 180 days	Distribution of modified Rankin Scale (mRS) score at 180 days in perampanel or placebo arms (mRS range 0 to 6, with higher scores indicating worse outcome)	180 days

External Links

•   Trial Website