Perampanel for Post-Cardiac Arrest Seizures

(PROSPER Trial)

Overseen By Edilberto Amorim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Disqualifiers: Acute cerebral hemorrhage, Pregnancy, Prisoner, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether perampanel can safely prevent seizures after a person's heart stops and restarts. Seizures often occur in cardiac arrest survivors and can cause further brain injury. Participants will receive either perampanel or a placebo to determine the treatment's effectiveness and safety. Suitable candidates have experienced a non-traumatic cardiac arrest outside the hospital, are in a coma upon arrival at Zuckerberg San Francisco General Hospital, and had their heartbeat return within 45 minutes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important 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 perampanel is likely to be safe for humans?

Research shows that perampanel is usually well-tolerated by patients. In earlier studies, perampanel was found to be safe and effective for treating seizures. For instance, one study found that people taking perampanel experienced fewer seizures compared to those taking a placebo, indicating its effectiveness without causing serious side effects.

Long-term users of perampanel have reported a significant drop in seizure activity. Another study found that many patients experienced a major reduction in seizures over several months. However, like any medication, some individuals might experience side effects, especially when adjusting doses.

It is important to note that this trial is in the early stages, so the researchers are still assessing the safety of perampanel specifically for seizures after cardiac arrest. However, past evidence suggests that perampanel is generally safe for controlling seizures. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Perampanel for treating post-cardiac arrest seizures because it offers a unique approach compared to standard treatments like benzodiazepines or anti-seizure medications such as phenytoin. Perampanel works by blocking AMPA receptors, which play a crucial role in transmitting excitatory signals in the brain, potentially reducing seizure activity more effectively. Additionally, the treatment regimen is short, with an initial oral load followed by a few days of daily doses, which could lead to quicker stabilization of patients. This new mechanism of action and the potential for rapid results make Perampanel a promising option for improving outcomes in patients experiencing seizures after cardiac arrest.

What evidence suggests that perampanel might be an effective treatment for post-cardiac arrest seizures?

Research has shown that perampanel can help reduce seizures. One study reported a 77% to 90% decrease in seizure frequency among participants over 9 months to 2 years. Another study found that 64.9% of patients experienced at least a 75% reduction in seizures after 180 days, with 36.8% becoming seizure-free. In this trial, participants will receive either perampanel or a placebo to evaluate its effectiveness in reducing post-cardiac arrest seizures. These findings suggest that perampanel could significantly lower the chance of seizures, potentially benefiting patients after a heart attack. ^{1 2 3 5 6}

Who Is on the Research Team?

Edilberto Amorim, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for patients who have survived a cardiac arrest but are at risk of developing seizures due to brain injury. It's not specified who can't join, so it's important to consult with the study team for exclusion criteria.

Inclusion Criteria

I was revived from a cardiac arrest in under 45 minutes.

I experienced a sudden cardiac arrest outside of a hospital without any injury causing it.

I was not able to follow commands upon hospital admission.

Exclusion Criteria

I have had a recent stroke or brain bleed.

My liver function tests are more than five times the normal limit.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either perampanel or placebo for post-cardiac arrest status epilepticus prevention

5 days

Daily administration in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days

Long-term follow-up

Neurological function assessed at 180 days post-treatment

180 days

What Are the Treatments Tested in This Trial?

Interventions

• Perampanel

Trial Overview The trial is testing whether Perampanel can prevent seizures after cardiac arrest. It's a pilot study, meaning it’s in early stages, and participants will be randomly assigned to either receive Perampanel or a placebo without active medication.

How Is the Trial Designed?

Group I: Perampanel Active Control 1 Intervention

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)

Group II: Placebo Placebo Group 2 Interventions

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)

Perampanel is already approved in European Union, United States for the following indications:

Approved in European Union as Fycompa for:

• Partial-onset epilepsy (with or without secondary generalized seizures)
• Primary generalized tonic-clonic seizures

Approved in United States as Fycompa for:

• Partial-onset seizures (with or without secondary generalized seizures)
• Primary generalized tonic-clonic seizures
• Monotherapy and adjunctive therapy for focal epilepsy (with or without secondary generalized seizures) in patients aged 4 years and older

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 113 patients with refractory focal-onset seizures, early add-on treatment with perampanel (PER) resulted in a 68.1% responder rate and a 26.5% seizure-free rate after 12 months, indicating its effectiveness as an adjunctive therapy.

The treatment was generally well-tolerated, with 30.1% of patients experiencing mild to moderate adverse events, primarily irritability and dizziness, suggesting a favorable safety profile for PER at a median dose of 6 mg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON). Abril Jaramillo, J., Estévez María, JC., Girón Úbeda, JM., et al.[2021]

In a 52-week observational study involving 483 patients with refractory epilepsy, perampanel was found to have a safety profile consistent with previous clinical studies, with 62.3% of patients reporting at least one treatment-emergent adverse event (TEAE), primarily mild to moderate in severity.

The most common clinically important TEAEs included dizziness (13.9%) and balance disorders (5.6%), with 31.7% of patients experiencing such events, indicating that while perampanel is effective, monitoring for these side effects is essential in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy. Maguire, M., Ben-Menachem, E., Patten, A., et al.[2022]

In a study of 77 patients with focal-onset seizures, perampanel (PER) as an early add-on therapy resulted in a 60% reduction in seizure frequency for over half of the participants after 12 months, with a retention rate of 79.2%.

PER was particularly effective for patients experiencing focal to bilateral tonic-clonic seizures, achieving a 60% seizure-free rate, although 40.3% of patients reported mild adverse events, leading to a 15.6% discontinuation rate due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel effectiveness and safety as early add-on treatment for focal-onset seizures: PEREAGAL study. Rodríguez-Osorio, X., Lema-Facal, T., Rubio-Nazábal, E., et al.[2022]

Perampanel, an anti-epileptic drug, may cause significant neuropsychiatric side effects, such as mood lability and psychosis, as observed in a case study of a 32-year-old male with generalized tonic-clonic seizures.

The patient's symptoms appeared to correlate with the administration of Perampanel, suggesting that its effects on the central nervous system could lead to complex interactions affecting mood and emotional regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel-Induced Cataplexy in a Young Male with Generalized Epilepsy. Kenaan, K., Zafar, M., Bond, R., et al.[2023]

Perampanel is a newly approved antiepileptic drug in the EU, specifically indicated for use as an additional treatment for partial-onset seizures in patients aged 12 and older.

It is designed to be used alongside other medications, highlighting its role as an adjunctive therapy in managing epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel: a new add-on treatment for epilepsy. [2021]

In the FAME study, perampanel was effective in reducing seizure frequency in patients with focal-onset seizures, with the highest efficacy observed at a low dose of 4 mg/day, regardless of the specific seizure type.

While treatment-emergent adverse events (TEAEs) were more common during the initial 12-week titration period (60.2%) compared to the 24-week maintenance period (28.4%), most TEAEs were self-limited or well-tolerated, indicating a favorable safety profile for perampanel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response. Kim, DW., Kim, JH., Lee, SK., et al.[2022]

Perampanel is an effective adjunctive treatment for patients aged 12 and older with primary generalized tonic-clonic seizures and partial-onset seizures, showing significant improvements in seizure control during phase III trials lasting 17 to 19 weeks, and sustained control for up to 4 years in some cases.

The drug is generally well tolerated, with most side effects being mild to moderate and related to the central nervous system, such as dizziness and fatigue, making it a viable option for patients with drug-resistant seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel: A Review in Drug-Resistant Epilepsy. Frampton, JE.[2021]

Perampanel has been shown to be effective in reducing seizure frequency in patients with epilepsy, demonstrating significant clinical efficacy in multiple studies.

The safety profile of perampanel indicates that while it is generally well-tolerated, it can cause side effects such as dizziness and fatigue, which should be monitored in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy. Greenwood, J., Valdes, J.[2020]

Citations

1. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06401707

PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac ... Secondary efficacy and safety endpoints include incidence of seizures and PCARSE, seizure frequency, time to seizure control, number of anti- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4283992/

Long-term safety of perampanel and seizure outcomes in ... Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1059131122001492

Perampanel as adjunctive therapy in drug resistant ... At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11827717/

Efficacy and safety of perampanel in patients with seizures ... After accounting for the titration of perampanel, median percent reduction in drop seizure frequency per 28 days during the Core Study ...

5. media-us.eisai.com media-us.eisai.com/2021-12-07-Eisai-Presents-Its-Largest-Real-World-Study-Of-Anti-Epileptic-Drug-FYCOMPA-R-perampanel-Across-Patient-Types-At-The-2021-American-Epilepsy-Society-AES-Annual-Meeting

Eisai Presents Its Largest Real-World Study Of Anti-Epileptic ... Eisai Inc. presented data from PERMIT, a large real-world clinical study evaluating its antiepileptic drug (AED) FYCOMPA® (perampanel) CIII, including as ...

6. fda.gov fda.gov/media/130828/download

Pediatric Postmarketing Pharmacovigilance Review 11 days after increasing the dose of perampanel from 2 to 4 mg daily for seizures. Medical history included traumatic brain injury at age 2 ...