levetiracetam and Emergencies

EcLiPSE (Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children) is a randomised controlled trial (RCT) in the United Kingdom. Challenges to success include the need to immediately administer an intervention without informed consent and changes in staffing during trial conduct, mainly due to physician rotations. Using literature on parents' perspectives and research without prior consent (RWPC) guidance, we developed an interactive training package (including videos, simulation and question and answer sessions) and evaluated its dissemination and impact upon on practitioners' confidence in recruitment and consent.. Questionnaires were administered before and immediately after training followed by telephone interviews (mean 11 months later), focus groups (mean 14 months later) and an online questionnaire (8 months before trial closure).. One hundred and twenty-five practitioners from 26/30 (87%) participating hospitals completed a questionnaire before and after training. We conducted 10 interviews and six focus groups (comprising 36 practitioners); 199 practitioners working in all recruiting hospitals completed the online questionnaire. Before training, practitioners were concerned about recruitment and consent. Confidence increased after training for explaining (all scale 0-5, 95% CIs above 0 and p values < 0.05): the study (66% improved mean score before 3.28 and after 4.52), randomisation (47% improvement, 3.86 to 4.63), RWPC (72% improvement, 2.98 to 4.39), and addressing parents' objections to randomisation (51% improvement, 3.37 to 4.25). Practitioners rated highly the content and clarity of the training, which was successfully disseminated. Some concerns about staff availability for training and consent discussions remained.. Training improved practitioners' confidence in recruitment and RWPC. Our findings highlight the value of using parents' perspectives to inform training and to engage practitioners in trials that are at high risk of being too challenging to conduct.

Topics: Emergencies; Humans; Informed Consent; Levetiracetam; Patient Selection; Phenytoin; Research Design; Status Epilepticus

Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.. This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.. This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.. ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134.

Topics: Adolescent; Age Factors; Anticonvulsants; Child; Child, Preschool; Clinical Protocols; Emergencies; Female; Humans; Infant; Infusions, Intravenous; Intention to Treat Analysis; Ireland; Levetiracetam; Male; Phenytoin; Piracetam; Research Design; Status Epilepticus; Time Factors; Treatment Outcome; United Kingdom

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children.. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge.. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines.. Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Clinical Protocols; Emergencies; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Prospective Studies; Single-Blind Method; Status Epilepticus; Treatment Outcome

Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies.. Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered.. Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation.. LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Drug Tolerance; Emergencies; Epilepsy; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus