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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\u2009months. Secondary outcomes include cognitive functioning after 18\u2009months, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2009years 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\u2009months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18\u2009months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ISRCTN,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.isrctn.com\/ISRCTN42686094\">ISRCTN42686094<\/jats:ext-link>\n                      . Registered on 24 May 2013.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-020-04874-2","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T09:05:23Z","timestamp":1606122323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicentre randomised controlled clinical trial (RESCUE ESES*)"],"prefix":"10.1186","volume":"21","author":[{"name":"on behalf of the RESCUE ESES study group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"van den Munckhof","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Arzimanoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen C.","family":"van Teeseling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans S. 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Changes in the study protocol have been\/will be proposed to ethics committees\/institutional review boards, communicated to trial site principal investigators by email and in regular investigator meetings (online meetings and meetings at international congresses). Depending on the implications of the changes, these have been\/will also be communicated to patients\/parents and the trial registry (ISRCTN). Since the first approval of the study protocol, two amendments have been submitted (approved in January 2016 and February 2018). These amendments had no impact on the patients that were already included in the study. Patients were included in the study if informed consent was obtained by their parents\/legal representatives as described in the \u201c\n                      \n                      \u201d section (subheading \u201c\n                      \n                      \u201d). The trial is conducted in accordance with the principles of the Declaration of Helsinki, as amended by the World Medical Association General Assembly in October 2013, with the ICH guidelines for Good Clinical Practice (CPMP\/ICH\/135\/95, July 1996) and with all international laws and regulations (including EU Clinical Trial Directive 2001\/20\/EC) and national laws and regulations of the countries in which the clinical trial is performed. The protocol (version 11, 25 November 2014) has been prepared and reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist (Additional file\n                      \n                      ).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"957"}}