Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.

To cite: Bacon M, Appleton R, Bangalore H, et al. Arch Dis Child Educ Pract Ed Epub ahead of print: [please include Day Month Year]. doi:10.1136/ archdischild2021323351 © Author(s) (or their employer(s)) 2022. No commercial reuse. See rights and permissions. Published by BMJ. BACKGROUND Convulsive status epilepticus (CSE) (box 1) is the most common childhood medical neurological emergency, with an incidence of approximately 20 per 100 000 per year in the developed world. 2 CSE can be fatal, but mortality is lower in children than in adults—at about 2%–7%. Adverse neurological consequences following CSE consist of subsequent epilepsy, motor deficits, and learning and behavioural difficulties. The main determinant of outcome is the underlying aetiology (box 2). There is low risk of morbidity and mortality in children with unprovoked/prolonged febrile CSE. This risk increases significantly in cases with structural or genetic causes.

BACKGROUND:Levetiracetam (Keppra®, UCB Pharma Ltd, Slough, UK) and zonisamide (Zonegran®, Eisai Co. Ltd, Tokyo, Japan) are licensed as monotherapy for focal epilepsy, and levetiracetam is increasingly used as a first-line treatment for generalised epilepsy, particularly for women of childbearing age. However, there is uncertainty as to whether or not they should be recommended as first-line treatments owing to a lack of evidence of clinical effectiveness and cost-effectiveness. OBJECTIVES:To compare the clinical effectiveness and cost-effectiveness of lamotrigine (Lamictal®, GlaxoSmithKline plc, Brentford, UK) (standard treatment) with levetiracetam and zonisamide (new treatments) for focal epilepsy, and to compare valproate (Epilim®, Sanofi SA, Paris, France) (standard treatment) with levetiracetam (new treatment) for generalised and unclassified epilepsy. DESIGN:Two pragmatic randomised unblinded non-inferiority trials run in parallel. SETTING:Outpatient services in NHS hospitals throughout the UK. PARTICIPANTS:Those aged ≥ 5 years with two or more spontaneous seizures that require anti-seizure medication. INTERVENTIONS:Participants with focal epilepsy were randomised to receive lamotrigine, levetiracetam or zonisamide. Participants with generalised or unclassifiable epilepsy were randomised to receive valproate or levetiracetam. The randomisation method was minimisation using a web-based program. MAIN OUTCOME MEASURES:The primary outcome was time to 12-month remission from seizures. For this outcome, and all other time-to-event outcomes, we report hazard ratios for the standard treatment compared with the new treatment. For the focal epilepsy trial, the non-inferiority limit (lamotrigine vs. new treatments) was 1.329. For the generalised and unclassified epilepsy trial, the non-inferiority limit (valproate vs. new treatments) was 1.314. Secondary outcomes included time to treatment failure, time to first seizure, time to 24-month remission, adverse reactions, quality of life and cost-effectiveness. RESULTS:Focal epilepsy. A total of 990 participants were recruited, of whom 330 were randomised to receive lamotrigine, 332 were randomised to receive levetiracetam and 328 were randomised to receive zonisamide. Levetiracetam did not meet the criteria for non-inferiority (hazard ratio 1.329) in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio vs. lamotrigine 1.18, 97.5% confidence interval 0.95 to 1.47), but zonisamide did meet the criteria (hazard ratio vs. lamotrigine 1.03, 97.5% confidence interval 0.83 to 1.28). In the per-protocol analysis, lamotrigine was superior to both levetiracetam (hazard ratio 1.32, 95% confidence interval 1.05 to 1.66) and zonisamide (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73). For time to treatment failure, lamotrigine was superior to levetiracetam (hazard ratio 0.60, 95% confidence interval 0.46 to 0.77) and zonisamide (hazard ratio 0.46, 95% confidence interval 0.36 to 0.60). Adverse reactions were reported by 33% of participants starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide. In the economic analysis, both levetiracetam and zonisamide were more costly and less effective than lamotrigine and were therefore dominated. Generalised and unclassifiable epilepsy. Of 520 patients recruited, 260 were randomised to receive valproate and 260 were randomised to receive to levetiracetam. A total of 397 patients had generalised epilepsy and 123 had unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio 1.19, 95% confidence interval 0.96 to 1.47; non-inferiority margin 1.314). In the per-protocol analysis of time to 12-month remission, valproate was superior to levetiracetam (hazard ratio 1.68, 95% confidence interval 1.30 to 2.15). Valproate was superior to levetiracetam for time to treatment failure (hazard ratio 0.65, 95% confidence interval 0.50 to 0.83). Adverse reactions were reported by 37.4% of participants receiving valproate and 41.5% of those receiving levetiracetam. Levetiracetam was both more costly (incremental cost of £104, 95% central range -£587 to £1234) and less effective (incremental quality-adjusted life-year of -0.035, 95% central range -0.137 to 0.032) than valproate, and was therefore dominated. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year, levetiracetam was associated with a probability of 0.17 of being cost-effective. LIMITATIONS:The SANAD II trial was unblinded, which could have biased results by influencing decisions about dosing, treatment failure and the attribution of adverse reactions. FUTURE WORK:SANAD II data could now be included in an individual participant meta-analysis of similar trials, and future similar trials are required to assess the clinical effectiveness and cost-effectiveness of other new treatments, including lacosamide and perampanel. CONCLUSIONS:Focal epilepsy - The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy. Generalised and unclassifiable epilepsy - The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. For women of childbearing potential, these results inform discussions about the benefit (lower teratogenicity) and harm (worse seizure outcomes and higher treatment failure rate) of levetiracetam compared with valproate. TRIAL REGISTRATION:Current Controlled Trials ISRCTN30294119 and EudraCT 2012-001884-64. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 75. See the NIHR Journals Library website for further project information.

Background Key challenges to the successful conduct of The Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE) trial were identified at the pre-trial stage. These included practitioner anxieties about conducting research without prior consent (RWPC), inexperience in conducting an ED-led trial and use of a medication that was not usual ED practice. As part of an embedded study, we explored parent and practitioner experiences of recruitment, RWPC and conduct of the trial to inform the design and conduct of future ED-led trials. Methods A mixed-methods study within a trial involving (1) questionnaires and interviews with parents of randomised children, (2) interviews and focus groups with EcLiPSE practitioners and (3) audio-recorded trial discussions. We analysed data using thematic analysis and descriptive statistics as appropriate. Results A total of 143 parents (93 mothers, 39 fathers, 11 missing information) of randomised children completed a questionnaire and 30 (25 mothers, 5 fathers) were interviewed. We analysed 76 recorded trial recruitment discussions. Ten practitioners (4 medical, 6 nursing) were interviewed, 36 (16 medical, 20 nursing) participated in one of six focus groups. Challenges to the success of the trial were addressed by having a clinically relevant research question, pragmatic trial design, parent and practitioner support for EcLiPSE recruitment and research without prior consent processes, and practitioner motivation and strong leadership. Lack of leadership negatively affected practitioner engagement and recruitment. EcLiPSE completed on time, achieving its required sample size target. Conclusions Successful trial recruitment and conduct in a challenging ED-led trial was driven by trial design, recruitment experience, teamwork and leadership. Our study provides valuable insight from parents and practitioners to inform the design and conduct of future trials in this setting.

BACKGROUND:Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS:This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS:990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION:These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING:National Institute for Health Research Health Technology Assessment programme.

Summary When developing a new medicine for children, the potential to extrapolate from adult efficacy data is well recognized. However, significant assumptions about the similarity of adults and children are needed for extrapolations to be biologically plausible. One such assumption is that of similar exposure–response (E–R-) relationships. Motivated by applications to antiepileptic drug development, we consider how data that are available from existing trials of adults and adolescents can be used to quantify prior uncertainty about whether E–R-relationships are similar in adults and younger children. A Bayesian multivariate meta-analytic model is fitted to existing E–R-data and adjusted for external biases that arise because these data are not perfectly relevant to the comparison of interest. We propose a strategy for eliciting expert prior opinion on external biases. From the bias-adjusted meta-analysis, we derive prior distributions quantifying our uncertainty about the degree of similarity between E–R-relationships for adults and younger children. Using these we calculate the prior probability that average pharmacodynamic responses in adults and younger children, both on placebo and at an effective concentration, are sufficiently similar to justify a complete extrapolation of efficacy data. A simulation study is performed to evaluate the operating characteristics of the approach proposed.

Convulsive status epilepticus is the most common life-threatening neurological emergency in childhood. Mortality is low but morbidity is not, which could substantially affect the child, their family, and health and social care systems. The cause and the management of convulsive status epilepticus are the two most important factors in determining its outcome. 1 Chin RF Neville BG Peckham C Bedford H Wade A Scott RC Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006; 368: 222-229 Summary Full Text Full Text PDF PubMed Scopus (413) Google Scholar Benzodiazepines are the recommended first-line drug treatment of convulsive status epilepticus and for which reasonably good scientific evidence based on a number of randomised controlled trials exists to support their use. 2 McTague A Martland T Appleton R Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2018; 1CD001905 PubMed Google Scholar Intravenous phenytoin in the UK and fosphenytoin in the USA are the current recommended first-choice, second-line drug treatments in children aged 6 months and older, 3 Samuels M Wieteska S Advanced paediatric life support: a practical approach to emergencies. 6th edn. John Wiley & Sons, 2019 Google Scholar , 4 Epilepsies: diagnosis and management. Clinical guideline [CG137]. National Institute for Health and Care Excellence (NICE). https://www.nice.org.uk/guidance/cg137Date accessed: March 8, 2020 Google Scholar , 5 Glauser T Shinnar S Gloss D et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016; 16: 48-61 Crossref PubMed Scopus (607) Google Scholar but until recently, this choice has not been based on good randomised controlled trial evidence. Additionally, phenytoin, and, perhaps to a lesser degree, fosphenytoin, is known to be associated with severe and potentially fatal adverse side-effects. 8 Lyttle MD Rainford NEA Gamble C et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019; 393: 2125-2134 Summary Full Text Full Text PDF PubMed Scopus (113) Google Scholar Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trialChildren, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. Full-Text PDF

Introduction Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (NHS) use on the basis of information from short-term trials that demonstrate efficacy. These trials do not provide information about the longer term outcomes, which inform treatment policy. This trial will assess the long-term clinical and cost-effectiveness of the newer treatment levetiracetam and zonisamide. Methods and analysis This is a phase IV, multicentre, open-label, randomised, controlled clinical trial comparing new and standard treatments for patients with newly diagnosed epilepsy. Arm A of the trial randomised 990 patients with focal epilepsy to standard AED lamotrigine or new AED levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from UK NHS outpatient epilepsy, general neurology and paediatric clinics. Included patients are aged 5 years or older with two or more spontaneous seizures requiring AED monotherapy, who are not previously treated with AEDs. Patients are followed up for a minimum of 2 years. The primary outcome is time to 12-month remission from seizures. Secondary outcomes include time to treatment failure (including due to inadequate seizure control or unacceptable adverse reactions); time to first seizure; time to 24-month remission; adverse reactions and quality of life. All primary analyses will be on an intention to treat basis. Separate analyses will be undertaken for each arm. Health economic analysis will be conducted from the perspective of the NHS to assess the cost-effectiveness of each AED. Ethics and dissemination This trial has been approved by the North West-Liverpool East REC (Ref. 12/NW/0361). The trial team will disseminate the results through scientific meetings, peer-reviewed publications and patient and public involvement. Trial registration numbers EudraCT 2012-001884-64; ISRCTN30294119 .

Background: Convulsive status epilepticus is the most common neurological emergency in children. Its management is important to avoid or minimise neurological morbidity and death. The current first-choice second-line drug is phenytoin (Epanutin, Pfizer Inc., New York, NY, USA), for which there is no robust scientific evidence. Objective: To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management. Design: A multicentre parallel-group randomised open-label superiority trial with a nested mixed-method study to assess recruitment and research without prior consent. Setting: Participants were recruited from 30 paediatric emergency departments in the UK. Participants: Participants aged 6 months to 17 years 11 months, who were presenting with convulsive status epilepticus and were failing to respond to first-line treatment. Interventions: Intravenous levetiracetam (40 mg/kg) or intravenous phenytoin (20 mg/kg). Main outcome measures: Primary outcome – time from randomisation to cessation of all visible signs of convulsive status epilepticus. Secondary outcomes – further anticonvulsants to manage the convulsive status epilepticus after the initial agent, the need for rapid sequence induction owing to ongoing convulsive status epilepticus, admission to critical care and serious adverse reactions. Results: Between 17 July 2015 and 7 April 2018, 286 participants were randomised, treated and consented. A total of 152 participants were allocated to receive levetiracetam and 134 participants to receive phenytoin. Convulsive status epilepticus was terminated in 106 (70%) participants who were allocated to levetiracetam and 86 (64%) participants who were allocated to phenytoin. Median time from randomisation to convulsive status epilepticus cessation was 35 (interquartile range 20–not assessable) minutes in the levetiracetam group and 45 (interquartile range 24–not assessable) minutes in the phenytoin group (hazard ratio 1.20, 95% confidence interval 0.91 to 1.60; p = 0.2). Results were robust to prespecified sensitivity analyses, including time from treatment commencement to convulsive status epilepticus termination and competing risks. One phenytoin-treated participant experienced serious adverse reactions. Limitations: First, this was an open-label trial. A blinded design was considered too complex, in part because of the markedly different infusion rates of the two drugs. Second, there was subjectivity in the assessment of ‘cessation of all signs of continuous, rhythmic clonic activity’ as the primary outcome, rather than fixed time points to assess convulsive status epilepticus termination. However, site training included simulated demonstration of seizure cessation. Third, the time point of randomisation resulted in convulsive status epilepticus termination prior to administration of trial treatment in some cases. This affected both treatment arms equally and had been prespecified at the design stage. Last, safety measures were a secondary outcome, but the trial was not powered to demonstrate difference in serious adverse reactions between treatment groups. Conclusions: Levetiracetam was not statistically superior to phenytoin in convulsive status epilepticus termination rate, time taken to terminate convulsive status epilepticus or frequency of serious adverse reactions. The results suggest that it may be an alternative to phenytoin in the second-line management of paediatric convulsive status epilepticus. Simple trial design, bespoke site training and effective leadership were found to facilitate practitioner commitment to the trial and its success. We provide a framework to optimise recruitment discussions in paediatric emergency medicine trials. Future work: Future work should include a meta-analysis of published studies and the possible sequential use of levetiracetam and phenytoin or sodium valproate in the second-line treatment of paediatric convulsive status epilepticus. Trial registration: Current Controlled Trials ISRCTN22567894 and European Clinical Trials Database EudraCT number 2014-002188-13. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 58. See the NIHR Journals Library website for further project information.

When developing a new medicine for children, the potential to extrapolate from adult efficacy data is well recognized. However, significant assumptions about the similarity of adults and children are needed for extrapolations to be biologically plausible. One such assumption is that of similar exposure–response ( E – R -) relationships. Motivated by applications to antiepileptic drug development, we consider how data that are available from existing trials of adults and adolescents can be used to quantify prior uncertainty about whether E – R -relationships are similar in adults and younger children. A Bayesian multivariate meta-analytic model is fitted to existing E – R -data and adjusted for external biases that arise because these data are not perfectly relevant to the comparison of interest. We propose a strategy for eliciting expert prior opinion on external biases. From the bias-adjusted meta-analysis, we derive prior distributions quantifying our uncertainty about the degree of similarity between E – R -relationships for adults and younger children. Using these we calculate the prior probability that average pharmacodynamic responses in adults and younger children, both on placebo and at an effective concentration, are sufficiently similar to justify a complete extrapolation of efficacy data. A simulation study is performed to evaluate the operating characteristics of the approach proposed.

BACKGROUND:Alternatives to prospective informed consent enable the conduct of paediatric emergency and critical care trials. Research without prior consent (RWPC) involves practitioners approaching parents after an intervention has been given and seeking consent for their child to continue in the trial. As part of an embedded study in the 'Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children' (EcLiPSE) trial, we explored how practitioners described the trial and RWPC during recruitment discussions, and how well this information was understood by parents. We aimed to develop a framework to assist trial conversations in future paediatric emergency and critical care trials using RWPC. METHODS:Qualitative methods embedded within the EcLiPSE trial processes, including audiorecorded practitioner-parent trial discussions and telephone interviews with parents. We analysed data using thematic analysis, drawing on the Realpe et al (2016) model for recruitment to trials. RESULTS:We analysed 76 recorded trial discussions and conducted 30 parent telephone interviews. For 19 parents, we had recorded trial discussion and interview data, which were matched for analysis. Parental understanding of the EcLiPSE trial was enhanced when practitioners: provided a comprehensive description of trial aims; explained the reasons for RWPC; discussed uncertainty about which intervention was best; provided a balanced description of trial intervention; provided a clear explanation about randomisation and provided an opportunity for questions. We present a seven-step framework to assist recruitment practice in trials involving RWPC. CONCLUSION:This study provides a framework to enhance recruitment practice and parental understanding in paediatric emergency and critical care trials involving RWPC. Further testing of this framework is required.

Aims Challenges to the success of ‘The Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE)’ trial included: practitioner anxieties about research without prior consent (‘deferred consent’), including how parents would react to being informed their child had already been randomised into the trial; inexperience in conducting an Emergency Department led trial in a paediatric neurological emergency; and use of an anti-epileptic medication (Levetiracetam), which was not the standard medication in this clinical setting. This was a nested study within EcLiPSE that aimed to explore parent and practitioner experiences to inform trial recruitment and conduct. Methods A mixed method study involving interviews, focus groups and questionnaires with EcLiPSE practitioners and questionnaires and interviews with parents of randomised children. Qualitative data were anonymised and analysed thematically. Quantitative data were cleaned and analysed using descriptive statistics and chi-square test for trend. We present key themes identified from data synthesis. Results One hundred and forty three parents (93 mothers, 39 fathers, 11 missing parent information) of randomised children completed a questionnaire and 30 (25 mothers, 5 fathers) were interviewed. Ten practitioners (4 medical, 6 nursing) were interviewed, 36 (16 medical, 20 nursing) participated in one of six focus groups and 199 (117 medical, 78 nursing, 3 ‘other’) completed a questionnaire in the final phase of EcLiPSE. Practitioners highly valued bespoke site training, a clinically important research question and simple trial design. These factors, alongside recruitment experience and leadership, were found to facilitate practitioner ‘buy in’, commitment and ultimately, trial success. Parents supported the trial and understood why consent had been sought after treatment had been given. EcLiPSE was completed on time, achieving its recruitment target. Conclusions Our study provides valuable insight into factors that helped to facilitate successful conduct and recruitment to a challenging emergency department led trial. The results will hopefully facilitate future research in paediatric emergency departments.

Cerebral palsy (CP) is not a disease, but a neurological syndrome, a combination of signs and symptoms, some of which may occur in neurodegenerative or metabolic disorders, particularly those with an onset in the first 2 years of life. There are many different causes of the syndrome. All children with CP should undergo brain MRI, even with an identified antenatal or perinatal insult. Children with CP should be referred to a paediatric neurologist or a clinical geneticist, or both, if appropriate and particularly in the absence of a known perinatal cerebral insult, with brain MRI that is reported to be normal, a progression in, or new, signs or where there is a reported ' family history of CP'. Finally, a few of the CP syndromes may be readily treatable and potentially prevent irreversible neurological and cognitive impairment.