EpiNet-First Trial 1: Comparison of efficacy of levetiracetam, lamotrigine and carbamazepine in people with previously untreated epilepsy who have focal seizures.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000643572
• Date of registration: 22/06/2015
• Prospective Registration: Yes
• Primary sponsor: EpiNet Study Group
• Public title: EpiNet-First Trial 1: Comparison of efficacy of levetiracetam, lamotrigine and carbamazepine in people with previously untreated epilepsy who have focal seizures.
• Scientific title: EpiNet First Trial 1: A pragmatic randomised controlled trial comparing the effectiveness of levetiracetam versus lamotrigine versus carbamazepine in people with previously untreated epilepsy who have focal seizures.
• Date of first enrolment: 28/07/2015
• Target sample size: 1467
• Recruitment status: Recruiting
• URL: https://anzctr.org.au/ACTRN12615000643572.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy;
• Phase: Phase 4

Countries of recruitment

Belgium, Georgia, India, Italy, Mexico, New Zealand, Slovenia, United Kingdom

Contacts

• Name: Dr Erica Beilharz

• Name: Dr Peter Bergin

Key inclusion & exclusion criteria

Inclusion criteria: The key inclusion criteria for EpiNet-Trial 1 is:

1-Aged 5 years or older on date of consent

2-The investigator is confident that the patient has epilepsy

3-Two or more spontaneous generalized seizures that require antiepileptic drug treatment (provided all seizures have not been absence seizures);

4-Antiepileptic drug monotherapy considered the most appropriate option

5-Willing to provide consent. For patients younger than the age of consent (usually 16 years), patient's parent/legal representative willing to give consent.
Exclusion criteria: 1-Provoked seizures (e.g. alcohol, recreational drugs)

2-Acute symptomatic seizures (e.g. acute brain haemorrhage or acute brain injury)

3-Absence seizures as only seizure type

4-Psychogenic non-epileptogenic seizures

5-Has ever been treated with an antiepileptic for more than one week

6-Known progressive neurological disease (e.g. brain tumour)

Age minimum: 5 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Neurological - Epilepsy

Epilepsy;
Epilepsy

Intervention(s)

EpiNet-First Trial 1: patients with focal seizures will be randomised (1:1:1) to receive levetiracetam or lamotrigine or carbamazepine.

Levetiracetam. Oral medication. Duration of treatment administration = 2 years. Dose to be determined by investigator according to usual clinical practice. The range of doses will vary from 250 mg to 4000 mg (oral tablets) daily in two divided doses and will be determined as considered clinically appropriate by the investigator. Adherence will be assessed by the investigators checking regularly with patients whether they are taking the drug as prescribed. Serum drug levels are not required as part of the study, but will be monitored as determined by the investigator and considered appropriate for good clinical care.

Lamotrigine. Oral medication. Duration of treatment administration = 2 years. Dose to be determined by investigator according to usual clinical practice. The range of doses will vary from 25 mg to 400 mg (oral tablets) daily in two divided doses and will be determined as considered clinically appropriate by the investigator.

Primary Outcome(s)

The primary endpoint for the EpiNet-First Trial 1 is time to 12 month remission from seizures; The outcome is assessed by self-reporting of seizures by participants.[The duration of the study is expected to be 5 years, with a 3 year recruitment period and a minimum 2 year follow-up period for each participant.]

Secondary Outcome(s)

Quality of life as assessed by the QOLIE31 and QOLIE48 questionnaires. These are validated, and are widely used in epilepsy research.[This is assessed at baseline (when the participant is enrolled) and at 3 , 6, 12 and 24 months.]

Time to 24 month remission. This outcome is assessed by self-reporting of seizures by participants.[From randomisation to 24 month remission. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Time to treatment failure due to inadequate seizure control. Treatment is deemed to have failed when the investigator changes the randomised anti-epileptic drug to a different anti-epileptic drug. [From randomisation to treatment failure due to inadequate seizure control. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Composite secondary outcome. Proportion of patients who achieve a seizure free 12 month remission by 18 months AND who have not changed to a different AED. This outcome is assessed by self-reporting of seizures by participants. [From randomisation to 18 months.]

Time to treatment failure due to unacceptable adverse events. Unacceptable adverse events may be either side effects (e.g. dizziness, fatigue, inablitlity to concentrate) which the participant and investigator agree are sufficiently incapacitating to warrant changing the drug, or abnormalities on examination or laboratory investigation (e.g. blood tests) that the investigator considers are sufficiently severe to terminate treatment. There are no study-specific tests which are mandated in the protocol; tests will be at the clinical discretion of the investigator.[From randomisation to treatment failure due to unacceptable adverse events. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Serious Adverse events attributed to the trial medication or other anti-epileptic medication. These are as follow: result in death
are life-threatening* (subject at immediate risk of death)
require in-patient hospitalisation or prolongation of existing hospitalisation; **
result in persistent or significant disability or incapacity, or
consist of a congenital anomaly or birth defect
Other important medical events***

*‘life-threatening’ in the definition of ‘serious’ refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.
**Hospitalisation is defined as an inpatient admission, regardless of length of stay, even if the hospitalisation is a precautionary measure for continued observation. Hospitalisations for a pre-existing condition, including elective procedures that have not worsened, do not constitute a Serious Adverse Event.
***Other important medical events that may not result in death, be life-threatening, or require hospitalisation may be considered a serious adverse event / experience when, based upon appropriate medical judgment, they may jeopardise the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
[From randomisation to onset of SAE. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Time to first seizure. This outcome is assessed by self-reporting of seizures by participants.[From Randomisation to first seizure. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Time to treatment failure, due to either inadequate seizure control, or due to unacceptable adverse events. Treatment is deemed to have failed when the investigator changes the randomised anti-epileptic drug to a different anti-epileptic drug. Unacceptable adverse events may be either side effects (e.g. dizziness, fatigue, inablitlity to concentrate) which the participant and investigator agree are sufficiently incapacitating to warrant changing the drug, or abnormalities on examination or laboratory investigation (e.g. blood tests) that the investigator considers are sufficiently severe to terminate treatment.[From randomisation to treatment failure. Participants will be followed for a minimum of 2 years up to 5 years post enrolment.]

Secondary ID(s)

Nil

Source(s) of Monetary Support

Neurological Foundation of New Zealand

Health Research Council of New Zealand

Julius Brendel Trust

Secondary Sponsor(s)

Auckland District Health Board

Ethics review

Status: Approved
Approval date:
Contact:

Northern B Health and Disability Ethics Committee