Comparative Effectiveness of Levetiracetam and Valproate Semisodium in Benzodiazepine-Resistant Status Epilepticus in Patients Aged 65 and Older

The primary objective of this study is to generate evidence for the treatment of **established status epilepticus** (eSE) in an elderly population, specifically targeting individuals aged 65 years or older who are experiencing convulsive or nonconvulsive benzodiazepine-resistant eSE. This is clinically relevant as it addresses a critical need for effective therapeutic strategies in a demographic that is often underrepresented in clinical research, thereby potentially improving outcomes and quality of life for this vulnerable group. The study involves the use of **levetiracetam** and **valproate semisodium**, both administered via infusion, to evaluate their effectiveness in this context.

The clinical trial focuses on individuals aged **65 years or older** who are experiencing **convulsive or nonconvulsive benzodiazepine-resistant status epilepticus**. The study population includes both male and female participants, and it is noted that the trial involves a vulnerable population. The sponsor has not provided the total number of participants. Participants were selected based on their ongoing condition of status epilepticus, which is resistant to treatment with benzodiazepines such as Lorazepam, Midazolam, Diazepam, or Clonazepam. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The primary objective is to generate evidence for the treatment of established status epilepticus in this elderly population.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study aimed at evaluating the effectiveness of intravenous **valproate semisodium** and **levetiracetam** in treating established status epilepticus (eSE) in individuals aged 65 years or older. The primary objective is to generate evidence for the treatment of eSE in this elderly population. The trial is set to run from February 2021 to November 2026, with the primary endpoint being the effectiveness of the trial drugs in terminating eSE and maintaining control of epileptic activity up to 60 minutes after the initiation of the intervention.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age and resistance to benzodiazepine treatment. The inclusion criteria specify that participants must be adults aged 65 or older with ongoing convulsive or nonconvulsive status epilepticus, as defined by specific clinical and EEG criteria. There are no principal exclusion criteria listed. Following the screening, participants will be randomly assigned to receive either valproate semisodium or levetiracetam via infusion.

The trial involves follow-up visits to monitor the participants' response to the treatment and to assess any adverse effects. The end-of-study visit will conclude the participant's involvement, which is expected to last for a maximum of one day, given the acute nature of the condition being treated. Conditions that may lead to early termination from the study include withdrawal of consent by the participant or the occurrence of significant adverse events that necessitate discontinuation of the trial intervention.

The clinical trial involves the administration of **LEVETIRACETAM**, a chemical compound used as an experimental medication. The pharmaceutical form of LEVETIRACETAM is identified as PHF00169MIG. It is administered via **infusion** with a maximum daily dose of 4.5 grams. The total dose is also capped at 4.5 grams, and the treatment period is limited to one day. LEVETIRACETAM is not a paediatric formulation and is not classified as an orphan drug. The active substance, also known as S-ETIRACETAM, is categorized under the ATC code N03AX14. Participant compliance with the dosing schedule will be monitored throughout the trial.

Another experimental medication used in the trial is **VALPROATE SEMISODIUM**, also known as DIVALPROEX SODIUM. This chemical compound is administered in the pharmaceutical form PHF00094MIG. Similar to LEVETIRACETAM, VALPROATE SEMISODIUM is delivered via **infusion**. The maximum daily and total dose for this medication is 3 grams, with the treatment period also restricted to one day. VALPROATE SEMISODIUM is not a paediatric formulation and does not have orphan drug status. It is classified under the ATC code N03AG01. Compliance with the administration schedule will be closely monitored to ensure adherence to the trial protocol.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The trial aims to generate evidence for the treatment of established status epilepticus in an elderly population, with both medications being tested for their effectiveness in this context.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the effectiveness of intravenous **valproate** (VPA) or **levetiracetam** (LEV) in terminating established status epilepticus (eSE) and maintaining control of epileptic activity up to 60 minutes after the initiation of the trial intervention. The trial is designed as a prospective, randomized, double-blind comparative effectiveness study, focusing on an elderly population with ongoing convulsive or nonconvulsive status epilepticus. The primary endpoint will be measured by observing the cessation of epileptic activity and the maintenance of control within the specified timeframe. Data collection will occur at the point of intervention and will be analyzed to determine the comparative effectiveness of the two treatments in achieving the desired clinical outcome.