Levetiracetam + Lacosamide for Seizure Prevention

(SEIZE-TBI Trial)

Overseen By Rita Brintzenhoff, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: Seizure prophylaxis

Must not be taking: Anti-seizure, Anti-epileptic

Disqualifiers: Seizures, Alcohol withdrawal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

600 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking anti-seizure or anti-epileptic medications, you will need to stop them to participate in this trial.

What data supports the effectiveness of the drug combination of Levetiracetam and Lacosamide for seizure prevention?

Research shows that Lacosamide, when added to Levetiracetam, can be effective for patients with epilepsy who do not respond well to other treatments. Lacosamide has been shown to reduce the frequency of seizures and improve quality of life in patients with difficult-to-control seizures. ^{1 2 3 4 5}

Is the combination of Levetiracetam and Lacosamide safe for humans?

Levetiracetam is generally considered safe and well-tolerated, with few drug interactions and no major side effects reported in studies. Lacosamide has been used in combination with Levetiracetam for epilepsy, and while specific safety data for the combination is limited, both drugs individually have shown good safety profiles in various studies. ^{1 6 7 8 9}

How is the drug combination of Levetiracetam and Lacosamide unique for seizure prevention?

This drug combination is unique because it combines Levetiracetam, which works by stabilizing electrical activity in the brain, with Lacosamide, which enhances the slow inactivation of sodium channels (pathways that help transmit electrical signals in the brain). This combination may offer a novel approach for patients whose seizures are not well-controlled with other treatments. ^{1 4 6 10 11}

What is the purpose of this trial?

The purpose of this study is to assess the incidence of early post-traumatic seizures. The study will also assess the benefit of lacosamide compared to levetiracetam in regards to agitation and behavioral adverse effects in patients with moderate to severe traumatic brain injury requiring seizure prophylaxis.

Research Team

Rita Brintzenhoff, MD

Principal Investigator

Atrium Health Carolina Medical Center

Eligibility Criteria

This trial is for individuals with moderate to severe traumatic brain injury who need treatment to prevent seizures. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or medications that could interfere with the study.

Inclusion Criteria

Patients admitted into the trauma team service

I started seizure prevention medication within a day after my injury.

I have been diagnosed with a moderate to severe brain injury.

Exclusion Criteria

Patients with a history of alcohol withdrawal or experiencing alcohol withdrawal that require medication treatment

Death, withdrawal of life support or transfer to hospice within 24 hours of injury

Special population (pregnant, incarcerated)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Within 24 hours post-injury

Treatment

Participants receive either levetiracetam or lacosamide for seizure prophylaxis

7 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days post-injury

Long-term monitoring

Monitoring for late post-traumatic seizures and other outcomes

Day 8 through day 30

Treatment Details

Interventions

• Lacosamide
• Levetiracetam

Trial Overview The trial is testing two drugs, levetiracetam and lacosamide, to see which one better prevents seizures after a traumatic brain injury. It will also compare how each drug affects patients' agitation and behavior.

Participant Groups

Group I: levetiracetam Experimental Treatment 1 Intervention

levetiracetam 1000 mg intravenously or by mouth twice daily for a total of 7 days

Group II: lacosamide Experimental Treatment 1 Intervention

lacosamide 200 mg intravenously or by mouth twice daily for a total of 7 days

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

Lacosamide was generally well tolerated in adults with cerebrovascular epilepsy etiology (CVEE), with common treatment-emergent adverse events including headache, dizziness, and fatigue, reported by 74.1% of patients on lacosamide.

In terms of efficacy, a higher proportion of patients on lacosamide completed 6 and 12 months of treatment without seizures compared to those on carbamazepine-CR, and during monotherapy, 56.7% of patients were 50% responders, with 20% achieving seizure freedom.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide in patients with epilepsy of cerebrovascular etiology. Rosenow, F., Brandt, C., Bozorg, A., et al.[2020]

Levetiracetam is an effective antiepileptic drug that can be used both as an add-on treatment and as a standalone therapy, demonstrating a broad spectrum of activity in suppressing seizures, supported by clinical trials and community practice.

It is safe, well-tolerated, and has a favorable pharmacokinetic profile, allowing for twice-daily dosing with minimal drug interactions, while also showing potential neuroprotective effects that may help slow disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levetiracetam: treatment in epilepsy. Ben-Menachem, E.[2019]

In a review of 67 studies involving 3,174 children treated with Levetiracetam (LEV) for epilepsy, the most common adverse events (AEs) reported were behavioral problems (10.9%) and somnolence (8.4%).

Children receiving polytherapy (multiple medications) experienced significantly more AEs (64%) compared to those on monotherapy (22%), with a higher rate of treatment discontinuation due to these AEs, particularly behavioral issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Levetiracetam in Paediatrics: A Systematic Review. Egunsola, O., Choonara, I., Sammons, HM.[2022]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

LACONORTE study: Efficacy and security of lacosamide as first add-on therapy for focal-onset epilepsy in real-life setting. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Lacosamide: new adjunctive treatment option for partial-onset seizures. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. [2018]

5. Denmark pubmed.ncbi.nlm.nih.gov

Lacosamide in patients with epilepsy of cerebrovascular etiology. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Sodium channel blockers are effective for benign infantile epilepsy. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Levetiracetam: treatment in epilepsy. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Levetiracetam as an Add-on Therapy for Symptomatic Refractory Epilepsy Treated in a Department of Neurosurgery]. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of Levetiracetam in Paediatrics: A Systematic Review. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy in patients with uncontrolled partial-onset seizures treated with adjunctive lacosamide: results from a Phase III open-label extension trial. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. [2018]