PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest (PROSPER)

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.

Study Overview

• Status: Recruiting
• Conditions: Seizures; Heart Arrest; Status Epilepticus
• Intervention / Treatment: Drug: Placebo; Drug: Perampanel

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.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Edilberto Amorim, MD; Phone Number: 628-206-3203; Email: prosperstudy@ucsf.edu
• Study Contact Backup: Name: Kevin Bao, BA; Email: prosperstudy@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Recruiting
      • Zuckerberg San Francisco General Hospital
      • Contact: Edilberto Amorim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Perampanel; Perampanel oral load of 24mg upon randomization followed by 8mg oral dose daily for four more days (second dose one day after load and total treatment duration is 5 days)	Drug: Perampanel; Perampanel is a non-competitive AMPA glutamate receptor antagonist.; Other Names: Fycompa
Placebo Comparator: Placebo; Placebo oral load upon randomization followed by daily placebo oral dose administration for four more days (second dose one day after load and total placebo administration duration is 5 days)	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of perampanel	percentage of participants who are able to complete the 5-day course of perampanel or placebo.	7 days
Adverse and Serious Adverse Events	percentage of participants with treatment-related adverse and serious adverse events in perampanel or placebo arms.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of post-cardiac arrest seizures	percentage of participants with post-cardiac arrest seizures in perampanel or placebo arms.	7 days
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
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
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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Edilberto Amorim, MD, University of California, San Francisco

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Trial Website

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): October 20, 2026

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 7, 2024

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: prophylaxis; seizure; status epilepticus; heart arrest
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Heart Arrest; Seizures; Status Epilepticus
• Other Study ID Numbers: 23-39712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes