The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy

The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy: A Randomized, Open Label Clinical Trial in Dhaka Medical College Hospital

Epilepsy is a serious chronic brain disorder that has a tendency towards recurrent seizures. This affects millions of people throughout the world and brings a heavy socioeconomic burden. The treatment of focal epilepsy is more challenging. Selecting an appropriate antiepileptic drug (AED) remains difficult because the chosen drug must be effective, safe and tolerable. It is important to consider the safety and efficacy of an AED for monotherapy separately. The goal of AED therapy is to achieve seizure control with little or no adverse efects, improve the patient's quality of life and ensure patient satisfaction. Different AEDs can be used to treat focal seizures in adults. First line medication for treating focal seizures is carbamazepine (CBZ), but it has drawbacks such as adverse effects including Steven Johnson syndrome, drug interactions and blood dyscrasia. There is also genetic linkage that Steven-Johnson syndrome and toxic epidermal necrolysis with carbamazepine are more common in individuals of Asian descent who carry the HLA-B 1502 allele. Another 1st line drug is lamotrigine (LTG) , it has favourable side effect profile including less sedative effect, less cognitive impairment, less drug interactions and blood dyscrasia. It has an elimination half- life longer than 24 hour, so once daily dosing is possible and it is associated with good drug compliance. Because of its favorable pharmacokinetics and side effect profile, LTG may be preferred to CBZ for focal epileptic seizures. In a study showed that the seizure freedom rate at the end of 6 months was 65% in LTG group compared to 73% in CBZ group. 41% in CBZ group and 32% in LTG group had at least one adverse effects.

Few trials have compared the effectiveness and safety of LTG with CBZ as monotherapy for focal seizures worldwide. By far, no study has yet been conducted addressing the issue of efficacy and safety between lamotrigine and carbamazepine among focal epilepsy patients in the context of Bangladeshi population. Since the usage of LTG is less common in Bangladesh, comparative study of efficacy and safety of LTG versus CBZ will be expected to give more confidence for the use of the drug. Considering this, the study aims to assess the safety and efficacy of carbamazepine and lamotrigine among focal epilepsy patients. This study finding have an implication in the treatment protocol which will be beneficial for the patients and physicians as well.

Study Overview

• Status: Enrolling by invitation
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: Lamotrigine tablet; Drug: Carbamazepine-Containing Product in Oral Dose Form

Detailed Description

This prospective hospital based open label interventional study will be conducted in Dhaka Medical College Hospital, Dhaka after receiving approval of this protocol from ethical review committee of DMC. Patients who match the inclusion and exclusion criteria will be enrolled in the study by simple random sampling. A written informed consent will be taken from patients or from their legal attendants after describing the aim, purpose and procedure of the study. Focal epilepsy will be diagnosed according to the criteria of the Commission on Classification and Terminology of the International League against Epilepsy (2017). In this study patients will be divided into 2 groups on their antiepileptic medication. The screening procedure, randomization and drugs will be started at day 1. All the assessment will be completed at day 1 and will be considered as baseline. Randomization will be done at 1:1 into parallel group. Each group will include 34 patients. Group A will include focal epileptic patients on lamotrigine and group B will include focal epileptic patients on carbamazepine. A structured questionnaire will be completed by investigator from answers of participating patients or with the help of their legal attendants, to obtain information on demographic characteristics (age, gender, marital status, education, socioeconomic level etc) and outcome of drug intervention. The patients will maintain a diary during the whole period and ask to note down any seizure frequency with date, time, duration and adverse effects of drugs. During the data record keeping every patient will be evaluated initially by investigator and later independently evaluated by a consultant neurologist.

Lamotrigine will be given at starting dose 25 mg once daily for 2 weeks, then 50 mg once daily for next 2 weeks and carbamazepine will be given at starting dose 100 mg twice daily for 2 weeks, then 200 mg twice daily for next 2 weeks. In both drugs dose will be increased until seizure control or side effects develop.

Patients will be followed up at 1st month, 3rd month and 6th month after receiving medication and following outcome will be assessed: reduction of seizure frequency, seizure free period, hospital readmission, frequency of status epilepticus, all-cause mortality, adverse drug reactions. Patients will be followed up at epilepsy clinic / outpatient department (OPD) and those patients who fail to attend at epilepsy clinic / OPD, by telephonic interview. All the above information will be recorded in a data collection form consisting of relevant questionnaire. After completion, data analysis will be done by SPSS version 26 (Chicago, Illinois, USA).

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1000
    • Dhaka Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years regardless of gender.
• Newly diagnosed focal epilepsy patient with or without secondary generalization.
• Relapse following antiepileptic drug withdrawal or failure on treatment other than lamotrigine or carbamazepine.
• Willing to participate and give informed written consent.

Exclusion Criteria:

• Patient with generalized seizure.
• Cryptogenic or unknown onset seizure.
• Known hypersensitivity to medication.
• History of drug abuse.
• Patient with serious medical conditions such as cardiovascular diseases, hepatic failure, renal failure, malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lamotrigine; Starting dose 25mg once daily for 2 weeks, then 50 mg once daily for next 2 weeks . Then dose will be increased until seizure control or side effects develop (Maximum 500 mg/day)	Drug: Lamotrigine tablet; Lamotrigine: Starting dose 25mg once daily for 2 weeks, then 50 mg once daily for next 2 weeks . Then dose will be increased until seizure control or side effects develop (Maximum 500 mg/day).; Other Names: Lamitrin, Lamogin
Active Comparator: Carbamazepine; Starting dose 100mg twice daily for 2 weeks, then 200 mg twice daily for next 2 weeks. Then dose will be increased until seizure control or side effects develop (Maximum 1600 mg/day)	Drug: Carbamazepine-Containing Product in Oral Dose Form; Starting dose 100mg twice daily for 2 weeks, then 200 mg twice daily for next 2 weeks. Then dose will be increased until seizure control or side effects develop (Maximum 1600 mg/day).; Other Names: Tegretol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy and safety between lamotrigine and carbamazepine among focal epilepsy patients.	The measurement of a medicine desired effect under ideal conditions, such as clinical trial (European medicine agency). It is measured as treatment retention rate at the end of follow up and percentage in reduction of seizure frequency from the time of drug initiation	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of seizure frequency.	The frequency of seizure was calculated as the number of seizure events before initial visit and at every follow up visit. The difference of seizure frequency was calculated by subtracting number of events from the previous value. In epilepsy clinic patients are asked to maintain a diary of seizure events with date, time and duration which are kept written in patient record form.	6 month
Duration of seizure free period.	It will be evaluated as percentage of patients who are seizure free at the end of follow up period.	6 month
Hospital readmission after receiving intervention	In previously admitted patient, is there any readmission?	6 month
Rate of death among patients	Death during study period	6 month
Adverse drug reactions among two groups.	Any noxious, unintended and undesired effect (including an abnormal laboratory finding) of a drug which occurs at a dose used in humans for prophylactic, diagnostic or therapeutic purpose (WHO).	6 month

Collaborators and Investigators

• Sponsor: Dhaka Medical College
• Investigators: Principal Investigator: Dr Mohammad Osman, MBBS, MD Neurology Thesis; Study Chair: Kazi Gias Uddin Ahmed, MD, Associate professor, Dhaka Medical College; Study Director: Reaz mahmud, Dhaka Medical College

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): October 1, 2023
• Study Completion (Estimated): October 1, 2023

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 7, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Cytochrome P-450 CYP3A Inducers; Lamotrigine; Carbamazepine
• Other Study ID Numbers: ERC-DMC/ECC/2022/330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: demographic variables, primary and secondary outcomes
• IPD Sharing Time Frame: october 2023 to september 2024
• IPD Sharing Access Criteria: who work with focal epilepsy patients
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No