RESCUE ESES: a Randomized European trial of Steroids versus Clobazam Usage for Encephalopathy with Electrical Status Epilepticus in Sleep
| ISRCTN | ISRCTN42686094 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN42686094 |
| EudraCT/CTIS number | 2013-000531-27 |
| Secondary identifying numbers | 43510 |
- Submission date
- 15/04/2013
- Registration date
- 24/05/2013
- Last edited
- 18/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Encephalopathy with Electrical Status Epilepticus in Sleep (ESES) syndrome is a rare epilepsy syndrome of childhood that is characterized by disturbed electrical brain activity (epilepsy) in sleep and problems with cognition (attention, memory, language, etc.) or behavior. ESES resolves spontaneously in puberty, but cognitive problems often remain. Adequate treatment is mandatory to prevent or reverse these cognitive deficits. However, it is unknown which treatment is the best. Treatment with "standard" anti-epileptic drugs is not very effective. Some studies suggest that clobazam and steroid treatment may be the best option. The only way to prove which treatment is best is to let a lottery decide which treatment a child gets (randomization) and then compare the effects of both treatments. The aim of this study is to establish which treatment is best for children with ESES syndrome, by treating 130 children with ESES syndrome with steroids (inflammation inhibitors) or clobazam and evaluating change in cognitive functioning after 6 and 18 months.
Who can participate?
Children aged 2 up to 12 years with a recent diagnosis of ESES syndrome (within the past six months) can participate in our study.
What does the study involve?
Children will be randomly allocated to either receive corticosteroids or clobazam for six months.
What are the possible benefits and risks of participating?
We hope to prove which of the two treatments is best for children with ESES syndrome. Because these two treatments are also given outside of this study, there are no specific benefits or risks associated with participating. Side-effects of corticosteroids can be e.g. fluid retention and increased infection risk, while e.g. drowsiness and coordination problems can occur while using clobazam. In most cases these side-effects can easily be resolved by changing the dosage.
Where is the study run from?
The study is run from the Brain Center Rudolf Magnus, department of Pediatric Neurology, University Medical Center Utrecht in the Netherlands. Participating centers are located in other European Union countries and include Italy (Pavia), France (Paris, Lyon, Strasbourg), United Kingdom (London, Edinburgh, Glasgow), Belgium (Brussels, Leuven), Germany (Kehl, Freiburg, Kiel, Vogtareuth), Denmark (Dianalund), Finland (Helsinki), Romania (Bucharest), Bulgaria (Sofia) and Spain (Madrid).
When is the study starting and how long is it expected to run for?
February 2014 to July 2023
Who is funding the study?
The study is funded by the National Epilepsy Fund of the Netherlands (NEF) and the Wilhelmina research fund.
Who is the main contact?
Dr F.E. Jansen
f.e.jansen@umcutrecht.nl
Contact information
Scientific
University Medical Center Utrecht / Wilhelmina Children's Hospital
Department of Pediatric Neurology
Lundlaan 6
Utrecht
3584 AE Utrecht
Netherlands
| Phone | +31 88 75 543 41 |
|---|---|
| F.E.Jansen@umcutrecht.nl |
Study information
| Study design | Multi-center randomized controlled clinical trial with blinded outcome assessment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Corticosteroids or clobazam for ESES syndrome: a European, multicenter, randomized, controlled clinical trial |
| Study acronym | RESCUE ESES |
| Study hypothesis | 1. As compared with treatment with clobazam, treatment with steroids leads to a 25% increase in favourable outcome in children with Encephalopathy with Electrical Status Epilepticus in Sleep (ESES) syndrome 2. In children with atypical ESES syndrome, treatment with corticosteroids or clobazam also leads to cognitive improvement, with a superiority of steroids over clobazam 3. Pro-inflammatory cytokines are increased in patients with ESES syndrome and are potential biomarkers for disease activity and therapeutic outcome 4. Pulsed steroid therapy has the comparable efficacy and less side effects compared to continuous corticosteroid therapy in children with ESES syndrome On 28/02/2014 the anticipated start date was changed from 01/01/2014 to 01/02/2014. |
| Ethics approval(s) | 1. Medical Ethics Committee Utrecht, the Netherlands, December 2013, ref: 13-275/G-M 2. In the other participating countries approval pending |
| Condition | Encephalopathy with electrical status epilepticus in sleep (ESES syndrome) |
| Intervention | Corticosteroids (either methylprednisolone pulse therapy or continuous oral prednisolone, depending on local preference) or clobazam. |
| Intervention type | Other |
| Primary outcome measure | 1. Intelligence quotient, or developmental quotient 2. Cognitive sumscore Improvement is defined as significant when improved by at least 75% of the standard deviation. |
| Secondary outcome measures | Secondary outcomes will be evaluated after 6 and 18 months: 1. Individual absolute test results, and IQ scores 2. Spike wave index during Non-rapid eye movement (non-REM) sleep. Improvement is defined as a decrease to less than 25% 3. Seizure frequency. Improvement is defined as a reduction of 50% or more as compared with baseline 4. Safety and tolerability, as assessed by the occurrence of serious adverse events 5. Differences in pro-inflammatory cytokine levels in patients with ESES who respond to either treatment strategies compared to non responders Added 28/02/2014: 6. Assessment of global daily functioning assessed with a visual analogue scale (VAS, -5 to 5) |
| Overall study start date | 01/02/2014 |
| Overall study end date | 31/07/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 2 Years |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 130 |
| Total final enrolment | 45 |
| Participant inclusion criteria | 1. Age 2 to 12 years 2. A diagnosis within six months prior to study inclusion (preferentially as soon as possible) of either typical or atypical ESES syndrome (as defined in study protocol) 3. No previous treatment with anti-epileptic drugs in the context of ESES 4. No previous treatment with either clobazam or corticosteroids 5. No current treatment with carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin and pregabalin and no treatment with any of these drugs in the previous three months 6. Written informed consent by parents / legal representatives |
| Participant exclusion criteria | 1. Patients with a spike wave index during wakefulness of > 50% 2. Any condition that, in the investigators judgement, contraindicates the use of clobazam or corticosteroids |
| Recruitment start date | 21/07/2014 |
| Recruitment end date | 01/01/2023 |
Locations
Countries of recruitment
- Belgium
- Bulgaria
- Denmark
- Finland
- France
- Germany
- Italy
- Netherlands
- Romania
- Spain
- United Kingdom
Study participating centre
3584 AE Utrecht
Netherlands
Sponsor information
Hospital/treatment centre
PO Box 85500
Utrecht
3508 GA
Netherlands
| Phone | +31 88 75 555 55 |
|---|---|
| info@umcutrecht.nl | |
| Website | http://www.umcutrecht.nl/ |
"ROR" |
https://ror.org/0575yy874 |
Funders
Funder type
Charity
No information available
No information available
No information available
No information available
Results and Publications
| Intention to publish date | 31/07/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | After the end of the trial we will analyse the data and plan a publication in a high impact peer reviewed journal, expected in 2021. |
| IPD sharing plan | The datasets generated (research online) and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 23/11/2020 | 25/11/2020 | Yes | No |
| Results article | 08/12/2023 | 18/12/2023 | Yes | No |
Editorial Notes
18/12/2023: Publication reference added.
22/09/2023: The total final enrolment was added.
01/02/2021: The following changes have been made:
1. The recruitment end date has been changed from 30/06/2019 to 01/01/2023.
2.The overall trial end date has been changed from 31/12/2020 to 31/07/2023 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 31/12/2021 to 31/07/2024.
25/11/2020: Publication reference added.
29/01/2018: The following changes were made:
1. Recruitment start date was changed from 01/02/2014 to 21/07/2014.
2. Recruitment end date was changed from 31/12/2017 to 30/06/2019.
3. Overall trial end date was changed from 31/12/2017 to 31/12/2020.
4. Publication plan, intention to publish date and participant level data were added.
