A trial to prevent epilepsy in people having surgery for a meningioma brain tumour
| ISRCTN | ISRCTN14381346 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14381346 |
| EudraCT/CTIS number | 2022-002371-10 |
| IRAS number | 1005506 |
| Secondary identifying numbers | UoL001699, IRAS 1005506, CPMS 56466 |
- Submission date
- 04/11/2022
- Registration date
- 22/06/2023
- Last edited
- 02/08/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
STOP’EM is a study for adults with a meningioma that needs surgical removal and who have not had a seizure before. We want to know if a short course of an anti-epileptic drug (AED) started 1 day before surgery prevents seizures happening after surgery.
Meningioma are the commonest primary brain tumour. They grow from the lining of the brain. In the UK each year about 1600 people with a meningioma have surgery. Approximately 70% of people do not present with epileptic seizures, but after surgical removal, around 12% will have a seizure within 12 months. Seizures affect quality of life and lead to uncertainty about the future.
In patients who have never had a seizure, neurosurgeons don’t know whether giving an AED before surgery (prophylaxis) will prevent seizures. Some neurosurgeons use prophylaxis and others don’t.
STOP’EM will compare a well-established AED called levetiracetam, to a placebo (a capsule that looks the same but contains no active drug). STOP’EM will look at whether starting levetiracetam shortly before surgery as a preventative measure:
1. reduces the chance of having a seizure in the 12 months after surgery
2. allows more people to resume driving 12 months after surgery
3. affects the quality of life in patients
4. is cost-effective
Who can participate?
Adults who have a meningioma that needs surgical removal & who haven’t had a seizure before can take part. We will recruit 1004 patients. Patients will be assigned at random to either:
What does the study involve?
Group 1: levetiracetam for 14 days
Group 2: placebo for 14 days
Participants will follow the normal care pathway and will be followed up regularly for 12 months to assess if they develop seizures & to measure their quality of life.
What are the possible benefits and risks of participating?
Benefits:
We hope that the results from the study will help patients and doctors in the future when making decisions about treatment.
Risks:
Possible common side effects when people are taking levetiracetam are drowsiness, headache, fatigue and dizziness, many of which patients will experience after removal of a meningioma.
It is not possible to minimise these risks as they are potential side effects from an established drug (levetiracetam).
Where is the study run from?
Liverpool Clinical Trials Centre (UK)
When is the study starting and how long is it expected to run for?
Nnovember 2022 to September 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) Programme (UK)
Who is the main contact?
Priya Francis, stopem@liverpool.ac.uk
Prof Michael Jenkinson, michael.jenkinson@liv.ac.uk
Contact information
Public
University of Liverpool
2nd Floor Institute in the Park
Alder Hey Children’s NHSFT
Eaton Road
Liverpool
L12 2AP
United Kingdom
 ORCID ID |
0000-0001-9748-335X |
|---|---|
| Phone | +44 151 7951732 |
| stopem@liverpool.ac.uk |
Principal Investigator
Clinical Science Centre
Walton Centre
Liverpool
L9 7LJ
United Kingdom
| ORCID ID |
0000-0003-4587-2139 |
|---|---|
| Phone | +44 151 5253611 |
| michael.jenkinson@liv.ac.uk |
Study information
| Study design | Interventional double blind randomized parallel group placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma: a randomised controlled trial (STOP’EM) |
| Study acronym | STOP'EM |
| Study hypothesis | Primary objective: To determine whether 2 weeks prophylactic levetiracetam treatment reduces the risk of developing seizures within 12 months of surgical resection of newly-diagnosed seizure naïve meningioma compared to placebo Secondary objectives: 1. To improve the understanding of the safety of prophylactic levetiracetam 2. To determine whether prophylactic levetiracetam influences quality of life 3. To determine the 30-day morbidity and mortality associated with meningioma surgery |
| Ethics approval(s) | Approved 24/04/2023, London - Central Research Ethics Committee (3rd Floor, Barlow House, 4 Minshull Street, Manchester, M1 3DZ, United Kingdom; +44 207 104 8061; londoncentral.rec@hra.nhs.uk), ref: 22/LO/0868 |
| Condition | Intracranial meningioma and epilepsy |
| Intervention | Levetiracetam 250mg (IMP) or Placebo – Participant will take IMP/placebo twice a day (2 x 250mg capsules, morning and evening) for 14 days in total. Treatment will begin 24 hours prior to surgery (participant will be in hospital for 2-3 days, and at home for the remainder of the treatment period). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Levetiracetam |
| Primary outcome measure | Time to at least one seizure at 12 months post-surgery measured using patient records |
| Secondary outcome measures | Measured using patient records unless noted otherwise: 1. Time to first seizure 2. Time to first convulsive seizure 3. Time to first unprovoked seizure (seizure from day 8 onwards) 4. Driving under licence at 6 and 12 months 5. EQ-5D-5L at pre-surgery, 4-6 weeks post-surgery, 12 weeks post-surgery, 52 weeks post-surgery 6. Serious adverse reactions. Active monitoring of SARs will be from the period of randomisation until completion of IMP course, plus 1 week 7. Landriel Ibañez classification 30 days post-surgery |
| Overall study start date | 01/11/2022 |
| Overall study end date | 30/09/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 1004 |
| Participant inclusion criteria | 1. Newly-diagnosed meningioma on MRI 2. Seizure-naïve at presentation 3. Surgical resection of meningioma planned 4. Age ≥16 years 5. Written and informed consent |
| Participant exclusion criteria | 1. Posterior fossa meningioma 2. Previous history of epilepsy 3. Previous history of provoked seizures 4. Previous cranial neurosurgery for any cause 5. Renal failure (Chronic Kidney Disease [CKD] 4-5) 6. Use of anti-epileptic drug for another indication (e.g. trigeminal neuralgia) within 7 days preceding randomisation 7. Known hypersensitivity to levetiracetam, other pyrrolidone derivatives or any of the excipients 8. Actively breastfeeding 9. Weigh below 50kg (if aged 16 or 17 years) |
| Recruitment start date | 01/07/2024 |
| Recruitment end date | 01/07/2028 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
2nd Floor Institute in the Park
Alder Hey Children’s NHS Foundation Trust
Eaton Road
Liverpool
L12 2AP
United Kingdom
Sponsor information
University/education
University of Liverpool Clinical Directorate
Thompson Yates Building
Brownlow Hill
Liverpool
L3 5RB
England
United Kingdom
| Phone | +44 7717863747 |
|---|---|
| stopem@liverpool.ac.uk | |
| Website | http://www.liv.ac.uk/ |
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/02/2030 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities Access to raw data and right to publish freely by all investigators in study or by Independent Steering Committee on behalf of all investigators |
| IPD sharing plan | Anonymous data from the trial will be made available to share with external researchers. All requests for access to these data will be reviewed by the Sponsor and data controllers. stopem@liverpool.ac.uk |
Editorial Notes
02/08/2024: The following changes were made to the trial record:
1. The recruitment start date was changed from 30/03/2023 to 01/07/2024.
2. The recruitment end date was changed from 31/03/2027 to 01/07/2028.
3. The intention to publish date was changed from 30/09/2028 to 01/02/2030.
4. The ethics approval was added.
03/07/2023: Internal review.
04/11/2022: Trial's existence confirmed by NHS HRA.
