EpiNet-First Trials - For Health Professionals

Overview

The EpiNet–First group of trials comprise 5 independent but closely related, multicentre, randomised controlled trials in which levetiracetam will be compared with standard anti-epileptic drugs (AEDs) in patients with new onset epilepsy. The protocols are closely modelled on the SANAD-II trials, which are currently underway in Great Britain.

Trials will be open (unblinded) and pragmatic in design. Patients will be allocated to the different trials according to the type of seizures they experience. Patients will be followed for a minimum of 2 years.

The primary endpoint will be 12 months sustained seizure freedom.

The trials will commence in early 2015.

Patients will be randomised on line via the EpiNet platform, immediately after the patient has given consent. We will use the EpiNet platform to record all data. No separate CRFs will be utilised.

The EpiNet study group has received very little external funding for this trial. We are therefore not able to supply the drugs, and we will not provide funding to the different centres to enrol or follow individual patients.

The trials have been registered on the ANZCTR registry (Australia and New Zealand Clinical Trials Registry).

Inclusion Criteria

• People aged 5 years or older who have had two or more spontaneous seizures
• The investigator is confident that the diagnosis is  epilepsy (at least an 80% level of confidence)
• Patients cannot previously have been treated with an AED for epilepsy for more than one week
• Patients must provide consent to participate in the trial. For patients younger than the age of consent (usually 16 years), patient’s parent / legal representative will need  to give consent, and the patient should give assent (details may vary depending on country-specific requirements)

Exclusion Criteria:

• Patients whose seizures were secondary to alcohol or recreational drugs
• Patients who have had acute symptomatic seizures (eg due to an acute stroke or acute head injury,
• Patients who have known progressive neurological disease (e.g glioma).
• Patients who have already received treatment with an AED for more than one week.

EpiNet–First Trials

• EpiNet–FirstTrial 1         Patients with focal seizures will be randomised (1:1:1) to receive either levetiracetam or lamotrigine or carbamazepine.
• EpiNet–FirstTrial 2         Patients with generalised seizures will be randomised(1:1)  to receive either sodium valproate or levetiracetam.
• EpiNet–FirstTrial 3         If sodium valproate is deemed unsuitable (e.g. in women of childbearing age), then patients with generalised seizures will be randomised(1:1) to either lamotrigine or levetiracetam.
• EpiNet–FirstTrial 4         Patients with seizures of unknown nature will be randomised (1:1:1) to receive either levetiracetam, lamotrigine, or sodium valproate.
• EpiNet–FirstTrial 5         If sodium valproate is deemed unsuitable (e.g. in women of childbearing age), then patients with seizures of unknown nature will be randomised (1:1) to levetiracetam  or lamotrigine.

Seizure Types

For the purposes of these trials we want to restrict the trials for patients with generalised seizures (i.e. trials 2 and 3) so that we include only patients with genetic generalised epilepsy. The criteria for diagnosing generalised seizures for these trials, therefore, are:

No clinical features to suggest focal seizures, and either

• Generalised spike and wave on EEG, or
• Myoclonic seizures, or
• Generalised tonic clonic seizures alone with onset below age 30, provided that not all seizures have occurred from sleepIf someone has had a tonic clonic seizure, but these criteria are not met, then patients should be entered into one of the trials for patients with seizures of uncertain nature. In particular if it is unclear whether there may have been a focal onset to someone’s seizure, the seizure should be classified as “Epileptic seizure, uncertain if generalised or focal”

Medication and dosing

All trial medication will be prescribed in a formulation and at a dose deemed suitable by the treating physicians. Generic versions of AEDs can be prescribed.

Follow-Up

Follow-up data will be collected at 3, 6, 12, 18 and 24 months, and annually thereafter until the end of the trial. Patients need to be contacted at these times, though they do not necessarily need to be seen in a clinic.

Investigators

Adult or child neurologists, epileptologists and paediatricians with an interest in epilepsy are encouraged to apply to be investigators for these studies.

To be accredited as an investigator, physicians will need to meet the following conditions:

• agree to the principles underpinning the EpiNet collaboration. These are spelled out in the Memorandum of Understanding published on this site.
• demonstrate that they diagnose people with epilepsy, and diagnose focal and generalised seizures, in a similar way to other members of the EpiNet study group. This will involve participating in an accreditation process. (See below)
• demonstrate that they are familiar with principles of Good Clinical Practice (GCP).  Anyone who is not yet familiar with GCP principles can undergo a tutorial here.
• undertake a tutorial which shows how the website works. Click here to go to the demonstration site. You can log in using the name “epinetdemo” with the password ‘Ep1net’ (Note the upper-case ‘E’ and the numeral ‘1’). The tutorial can be found here.

We will also request that investigators send a copy of their CV to the coordinating centre in Auckland, New Zealand.

The principle investigator at each site, and/or a representative of the institution, should sign an agreement with the EpiNet steering group confirming the arrangements for the trials. A generic version of the form can be found here

Ethics approval

Investigators will need to obtain approval from their local ethics committee. The EpiNet team based in Auckland will be very happy to help with this process.

Accreditation

All investigators need to participate in an accreditation process to confirm that they diagnose people with epilepsy, and diagnose focal and generalised seizures, in a similar way to other members of the EpiNet study group. This involves assessing 12 or 18 case histories. Not all of the patients in the cases have epilepsy.

Click here to register.

Or contact the EpiNet administrator [email protected] for information regarding the accreditation process.

Monitoring

Data will be reviewed centrally by an independent data analyst to look for unusual patterns which might indicate erroneous or falsified data. Data from each centre will be compared with that obtained from other centres.

Centres will be required to forward to the coordinating centre copies of the informed consent documents and seizure diaries on selected patients. The entries made in the EpiNet records will be checked against these documents. The complete EpiNet records for these patients will be checked to ensure that the data is valid.

On site monitoring will be performed at the discretion of the EpiNet steering committee. It is anticipated that the sites from which most patients have been recruited will be visited by a site monitor.

Publication

We expect that separate reports will be published for each of the five EpiNet–First trials. All papers will be written on behalf of the EpiNet study group. The writing group will be determined by the trial steering committee. All investigators who enter a patient who completes the minimum follow-up period into a trial will be listed in an appendix as one of the paper’s authors. The investigators who enter the most patients into each trial will have their names listed at the head of the relevant paper(s).

If you would like to participate in these trials, please register your interest here:
[email protected]