TY - JOUR
T1 - Corticosteroids versus clobazam in epileptic encephalopathy with ESES
T2 - a European multicentre randomised controlled clinical trial (RESCUE ESES*)
AU - van den Munckhof, Bart
AU - Arzimanoglou, Alexis
AU - Perucca, Emilio
AU - van Teeseling, Heleen C
AU - Leijten, Frans S S
AU - Braun, Kees P J
AU - Jansen, Floor E
N1 - Funding Information:
This study is funded by the Dutch Epilepsy Fund (Epilepsiefonds, grant 13-17) and the Wilhelmina Children’s Hospital Research Fund (grant R2634). The funding sources had no direct involvement in the conduct of the study.
Funding Information:
The study is conducted by the RESCUE ESES study group which constitutes current and previous collaborators, and includes Anna Jansen (Brussels, Belgium), Patrick van Bogaert (Brussels, Belgium), Lieven Lagae (Leuven, Belgium), Guido Rubboli (Dianalund, Denmark), Eija Gaily (Helsinki, Finland), Pierangelo Veggiotti (at start of study working in Pavia, Italy; currently working in Milano, Italy), Gaetano Cantalupo (Verona, Italy), Giuseppe Gobbi (Bologna, Italy), Dana Craiu (Bucharest, Romania), Petia Dimova (Sofia, Bulgaria), Thomas Bast (Kehl, Germany), Julia Jacobs (Freiburg, Germany), Sarah von Spiczak (Schwentinental-Raisdorf, Germany), Anja Lübbig (Vogtareuth, Germany), Stéphane Auvin (Paris, France), Anne de Saint-Martin (Strasbourg, France), J. Helen Cross (London, UK), Richard Chin (Edinburgh, UK), Sameer Zuberi (Glasgow, UK), Irene Garcia Morales (Madrid, Spain), Georgia Ramantani (Zurich, Switzerland), and all authors of this manuscript. We thank all study participants and their parents/caregivers for their participation in the trial and their patience during the conduct of the study. We thank all co-investigators, collaborating paediatric neurologists, neuropsychologists, clinical neurophysiologists, technicians, nurses, outpatient assistants, laboratory employees, and anyone else involved in the conduct of the study for their efforts and support. We thank Dr. Guido Rubboli for his suggestions regarding the protocol for the registration of EEGs in the study. We thank Carolijn Kesler for her continued support in the legislatory and contractual challenges that we faced during the preparations and conduct of the study. We thank Eltje Bloemen for her general support and enthusiasm with the conduct of the trial, knowledge about Good Clinical Practice guidelines, approachability for ESES patients, and help with the international coordination of the study. We thank Judith Meester for her support with the conduct of the trial. The principal investigator and study coordinator will have full access to the final trial dataset. The trial results will be published by the members of the executive committee, on behalf of all participating centres. Additional analyses and sub-studies should be approved by the executive committee, and also be published on behalf of all participating investigators. One representative of each participating centre will be stated as co-author, and all participating physicians will constitute the study group and will be mentioned in the final publication of study results.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/11/23
Y1 - 2020/11/23
N2 - BACKGROUND: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomised controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and autoantibodies in serum.METHODS: The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. A total of 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomised in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation.DISCUSSION: The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomised controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome.TRIAL REGISTRATION: ISRCTN, ISRCTN42686094 . Registered on 24 May 2013.
AB - BACKGROUND: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomised controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and autoantibodies in serum.METHODS: The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. A total of 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomised in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation.DISCUSSION: The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomised controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome.TRIAL REGISTRATION: ISRCTN, ISRCTN42686094 . Registered on 24 May 2013.
KW - Clobazam
KW - Cognition
KW - Corticosteroids
KW - CSWS
KW - Epilepsy
KW - ESES
KW - Neuropsychology
KW - Sleep
UR - http://www.scopus.com/inward/record.url?scp=85096593606&partnerID=8YFLogxK
U2 - 10.1186/s13063-020-04874-2
DO - 10.1186/s13063-020-04874-2
M3 - Article
C2 - 33228736
SN - 1745-6215
VL - 21
SP - 1
EP - 11
JO - Trials
JF - Trials
IS - 1
M1 - 957
ER -