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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well two different drugs, levetiracetam and lacosamide, prevent seizures in individuals with moderate to severe brain injuries. Researchers aim to determine which drug is more effective and whether one causes fewer side effects, such as agitation or mood changes. Individuals who have recently sustained a brain injury and require medication to prevent seizures may be suitable candidates for this study. As a Phase 4 trial, this research focuses on understanding how these FDA-approved treatments can benefit a broader range of patients.

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 is the safety track record for these treatments?

Research has shown that both levetiracetam and lacosamide are generally safe and well-tolerated. Studies have found levetiracetam to be effective and safe, particularly when combined with other treatments for partial-onset seizures. One study significantly reduced the number of seizures. It is also considered safe for preventing seizures in adults with brain tumors.

Lacosamide is safe and well-tolerated, even with long-term use. Common side effects include sleepiness, dizziness, and fatigue, but no new safety issues have emerged with prolonged use.

Both treatments have FDA approval for managing epilepsy, supporting their safety for other uses. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using levetiracetam and lacosamide for seizure prevention because these drugs offer a new approach by combining two different mechanisms of action. Levetiracetam is unique because it modulates neurotransmitter release, while lacosamide enhances the slow inactivation of sodium channels. This dual action can potentially provide more comprehensive seizure control compared to standard treatments, which often rely on a single mechanism. Additionally, both drugs can be administered intravenously or orally, offering flexibility in treatment administration.

What evidence suggests that this trial's treatments could be effective for seizure prevention in traumatic brain injury?

This trial will compare levetiracetam and lacosamide for seizure prevention. Research has shown that both medications help reduce seizures. Participants may receive levetiracetam, which studies have found greatly lowers the number of seizures and outperforms placebos. It has succeeded in various situations, including preventing seizures in adults with brain tumors. Alternatively, participants may receive lacosamide, which is also effective, with evidence showing it significantly reduces seizures in users. It is well tolerated and considered a strong choice for managing epilepsy. Both treatments have a proven history of controlling and preventing seizures. ^{2 3 6 7 8}

Who Is on the Research Team?

Rita Brintzenhoff, MD

Principal Investigator

Atrium Health Carolina Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8677652/

Clinical Efficacy and Safety of Lacosamide as an ... Conclusions: Our results revealed that LCM adjunctive therapy even with long-term treatment was efficacious and well tolerated in adults with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0920121125001585

Real world observational study investigating clinical ... This study's findings suggest that LCM is an effective and well-tolerated treatment option for epilepsy management, offering a promising alternative for ...

3. neurology.org neurology.org/doi/10.1212/WNL.0000000000211118

The Safety and Efficacy of Adjunctive Lacosamide for ... The outcomes of efficacy included the proportion of participants who had a ≥50% and ≥75% decrease in seizure frequency (≥50% and ≥75% response ...

4. link.springer.com link.springer.com/article/10.1007/s10072-025-08563-3

Efficacy and safety of branded vs generic lacosamide in ... The primary study outcomes are shown in the Fig. 1 as follows: in Group A, 7 patients (23.3%) showed no change in seizure frequency, 18 patients ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1186768/full

Effectiveness and safety of Lacosamide therapy for ... Results showed that after 12 months of LCM treatment, seizure frequency decreased from 4.20 ± 8.05 to 0.39 ± 0.77, and the 50% responder rate, 75% responder ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8408586/

Long‐term safety and tolerability of lacosamide ... Overall, long‐term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.694381/full

Safety and Tolerability of Lacosamide in Patients With ... Conclusion: Lacosamide is generally safe and well tolerated in patients with epilepsy. Common AEs were sedation, dizziness, and fatigue. It is necessary to pay ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11647428/

Long‐term safety and efficacy of adjunctive lacosamide in ... Overall, the median percent reduction of GTCS was 88.6%; the 50% and 75% responder rates were 79.8% and 66.0%, respectively; and 58.4% of ...