Trial comparing the effectiveness and cost effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of Standard And New Antiepileptic Drugs
| ISRCTN | ISRCTN30294119 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN30294119 |
| EudraCT/CTIS number | 2012-001884-64 |
| Secondary identifying numbers | 12477 |
- Submission date
- 03/07/2012
- Registration date
- 03/07/2012
- Last edited
- 22/12/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Epilepsy is a condition that affects the brain and causes repeated seizures. Antiepileptic drugs (AED) are the mainstay of treatment and may have to be taken for life. The ultimate goal of treatment is to maximise quality of life by eliminating seizures at drug doses that do not cause side effects. However, for many patients there is a necessary trade-off between effective seizure control and side effects, which can diminish quality of life. Over the past 20 years, a number of new AED drugs have become available and have been approved for NHS use on the basis of information from short-term studies, but these studies do not provide information about the longer term outcomes. The aim of this study is to compare the effectiveness and cost-effectiveness of the AEDs levetiracetam and zonisamide compared with the standard treatments for epilepsy (lamotrigine and valproate).
Who can participate?
Children aged 5 or older and adults with epilepsy
What does the study involve?
This study is essentially two studies run in parallel. Patients with untreated focal onset seizures (affecting a small part of the brain) are randomly allocated to be treated with either lamotrigine, levetiracetam or zonisamide. Patients with generalised onset seizures (affecting both halves of the brain) or seizures that are difficult to classify are randomly allocated to be treated with either levetiracetam or valproate.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
University of Liverpool (UK)
When is the study starting and how long is it expected to run for?
August 2012 to February 2018
Who is funding the study?
NIHR Health Technology Assessment program (HTA) (UK)
Who is the main contact?
Silviya Balabanova
silviya.balabanova@liv.ac.uk
Contact information
Scientific
Molecular and Clinical Pharmacology Department
Clinical Sciences Centre
University of Liverpool
Lower Lane
Liverpool
L9 7LJ
United Kingdom
| Phone | +44 (0)151 529 5464 |
|---|---|
| sanad2@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Patient information sheets can be downloaded from http://www.sanad2.org.uk/families.html |
| Scientific title | A pragmatic randomised controlled trial comparing the effectiveness and cost effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of Standard And New Antiepileptic Drugs (SANAD-II) |
| Study acronym | SANAD-II |
| Study objectives | SANAD-II is a phase IV multicentre pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments (lamotrigine and valproate) for epilepsy. More details can be found at http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=12477 |
| Ethics approval(s) | NRES Committee North West Liverpool East, First MREC approval date 07/06/2012, ref: 12/NW/0361 |
| Health condition(s) or problem(s) studied | Topic: Medicines for Children Research Network, Neurological; Subtopic: All Diagnoses, Neurological (all Subtopics); Disease: Nervous system disorders |
| Intervention | SANAD-II will essentially be two randomised controlled trials run in parallel. Arm A of SANAD-II will compare lamotrigine, levetiracetam and zonisamide in patients with untreated focal onset seizures. Arm B of SANAD-II will compare levetiracetam and valproate in patients with generalised onset seizures or seizures that are difficult to classify. It will aim to accrue about 1510 patients (children aged 5 or older and adults) over a 3.5 year period and follow up will continue for a further two years (a maximum time a patient will receive randomised treatment is 5.5 years). There will be economy of scale given that the protocols and data structure are almost identical and that the same group of collaborators will be recruiting patients to both trials. There will be no competition for patients between Arm A and Arm B as the inclusion criteria are mutually exclusive. All treatments will be issued as per routine NHS. Arm A: Patients randomised to receive lamotrigine, levetiracetam or zonisamide Arm B: Patients randomised to receive levetiracetam or valproate Trial interventions will follow the usual clinical practice |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Lamotrigine, levetiracetam, zonisamide, valproate |
| Primary outcome measure | Time to 12 month remission from seizures. This is a time to event outcome, measured during the entirity of follow-up. |
| Secondary outcome measures | 1. Adverse events at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years 2. Quality of Life (QOL) outcomes at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years 3. Time to 24 month remission. This is a time to event outcome, measured during the entirity of follow-up 4. Time to first seizure. This is a time to event outcome, measured during the entirity of follow-up 5. Time to treatment failure due to inadequate seizure control. This is a time to event outcome, measured during the entirity of follow-up 6. Time to treatment failure due to unacceptable adverse events. This is a time to event outcome, measured during the entirity of follow-up 7. Time to treatment failure. This is a time to event outcome, measured during the entirity of follow-up |
| Overall study start date | 01/08/2012 |
| Completion date | 30/11/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 5 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1510; UK Sample Size: 1510 |
| Total final enrolment | 1510 |
| Key inclusion criteria | 1. Male and female aged 5 years or older 2. Two or more spontaneous seizures that require antiepileptic drug treatment 3. Untreated and not previously treated with antiepileptic drugs 4. Antiepileptic drug monotherapy considered the most appropriate option 5. Willing to provide consent (patients parent/legal representative willing to give consent where the patient is aged under 16 years of age) |
| Key exclusion criteria | 1. Provoked seizures (e.g. alcohol) 2. Acute symptomatic seizures (e.g. acute brain haemorrhage or brain injury) 3. Currently treated with antiepileptic drugs 4. Progressive neurological disease (e.g. known brain tumour) |
| Date of first enrolment | 01/08/2012 |
| Date of final enrolment | 01/02/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
L9 7LJ
United Kingdom
Sponsor information
University/education
Health Services Research
1-3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 30/11/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 26/08/2020 | 02/09/2020 | Yes | No |
| Results article | results for newly diagnosed focal epilepsy | 10/04/2021 | 13/04/2021 | Yes | No |
| Results article | results for newly diagnosed generalised and unclassifiable epilepsy | 10/04/2021 | 13/04/2021 | Yes | No |
| Other publications | sub study on methods | 05/07/2021 | 07/07/2021 | Yes | No |
| Results article | HTA report | 01/12/2021 | 22/12/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
22/12/2021: Publication reference added.
07/07/2021: Publication reference added.
13/04/2021: The following changes were made to the trial record:
1. Publication references added.
2. The total final enrolment was added.
02/09/2020: Publication reference added.
25/02/2019: The following changes have been made:
1. The intention to publish date has been added.
2. The trial website has been added.
3. The patient information sheet information has been updated.
4. The public contact details have been updated.
22/02/2019: The overall trial end date has been changed from 01/02/2018 to 30/11/2019.
