Clinical Study of Combination Therapy with Sodium Valproate and Lamotrigine for Pediatric Drug-Resistant Epilepsy

JRCT ID: jRCT1031240304

Registered date:28/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pediatric drug-resistant epilepsy
• Date of first enrollment: 28/08/2024
• Target sample size: 46
• Study type: Interventional

Intervention(s)

(Titration Phase) Start sodium valproate at 15 mg/kg/day 1-3 times daily, increasing to 25 mg/kg/day 1-3 times daily after 1 week. After 3 weeks of sodium valproate initiation, lamotrigine is gradually increased to 0.15 mg/kg/day once daily, 0.3 mg/kg/day once daily, 0.6 mg/kg/day twice daily, and 0.9 mg/kg/day twice daily every 2 weeks. The initial target dose is sodium valproate 25 mg/kg/day 1-3 times daily and lamotrigine 0.9 mg/kg/day twice daily. During the titration period, previously used antiepileptic drugs should, in principle, be tapered off.
(Maintenance Phase) Depending on the physical condition, the dose of sodium valproate may be increased to 25-35 mg/kg/day (5 mg/kg every 1-2 weeks, up to 1000 mg/day for boys and 600 mg/day for girls), lamotrigine may be increased to 0.9-3 mg/kg/day (0.3 mg/kg every 1-2 weeks, up to 200 mg/day).

Outcome(s)

• Primary Outcome: Percentage of seizures-free patients in the maintenance phase (52 weeks)

Secondary Outcome

(1) Percentage of seizure-free patients during the incremental phase (10 weeks) and the maintenance phase (52 weeks), for a total of 62 weeks.
(2) Percentage of patients who remained on the drug during the titration phase (10 weeks) and the maintenance phase (52 weeks), for a total of 62 weeks
(3) Comparison of efficacy by seizure type, epilepsy type, and epilepsy syndrome
(4) Changes in scalp EEG (30 minutes), number of abnormal epileptic waves, and background activity
(5) Side effects and safety evaluation
(6) Quality of life assessment using PedsQL

Key inclusion & exclusion criteria

• Age minimum: >= 4age old
• Age maximum: <= 15age old
• Gender: Both

Include criteria

(1) Boys 4-15 years old, girls 4-9 years old
(2) Patients with epilepsy who have one or more of the following types of seizures: focal onset seizures, focal bilateral tonic-clonic seizures (secondary generalization), generalized onset motor seizures, or unexplained onset motor seizures
(3) Patients who have failed to achieve seizure resolution with any two antiepileptic drugs except sodium valproate and lamotrigine
(4) Head MRI or CT, EEG, or blood tests within 1 year prior to enrollment
(5) Patients who have obtained written consent from a parent or guardian or a surrogate

Exclude criteria

(1) Metabolic or neurodegenerative disease is suspected
(2) Patients with hepatic dysfunction of moderate severity or greater (AST or ALT greater than 2.5 times the upper reference limit or total bilirubin greater than 1.5 times the upper reference limit)
(3) Patients with absence seizures, atypical absence seizures, or nonconvulsive status epilepticus
(4) Poor adherence to medication (generally assumed to take less than 70% of doses)
(5) Inability of the patient or family members to keep an epilepsy medication log
(6) Patients with a history of treatment with sodium valproate and lamotrigine combination therapy or monotherapy with either
(7) Patients who are deemed inappropriate as research subjects by the investigator or others

Related Information

• Primary Sponsor: Enokizono Takashi
• Source(s) of Monetary Support: University of Tsukuba Hospital