Clinical Trial

. 2016 Jun 15;6(6):e011565.

doi: 10.1136/bmjopen-2016-011565.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Anna Rosati¹, Lucrezia Ilvento¹, Manuela L'Erario², Salvatore De Masi³, Annibale Biggeri⁴, Giancarlo Fabbro⁴, Roberto Bianchi⁵, Francesca Stoppa⁶, Lucia Fusco⁷, Silvia Pulitanò⁸, Domenica Battaglia⁹, Andrea Pettenazzo¹⁰, Stefano Sartori¹¹, Paolo Biban¹², Elena Fontana¹³, Elisabetta Cesaroni¹⁴, Donatella Mora¹⁵, Paola Costa¹⁶, Rosanna Meleleo¹⁷, Roberta Vittorini¹⁸, Alessandra Conio¹⁹, Andrea Wolfler²⁰, Massimo Mastrangelo²¹, Maria Cristina Mondardini²², Emilio Franzoni²³, Kathleen S McGreevy²⁴, Lorena Di Simone²⁵, Alessandra Pugi³, Lorenzo Mirabile², Federico Vigevano⁷, Renzo Guerrini¹

Affiliations

¹ Paediatric Neurology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
² Intensive Care Unit, Meyer Children's Hospital, Florence, Italy.
³ Clinical Trial Office Meyer Children's Hospital, Florence, Italy.
⁴ Department of Statistics, 'G Parenti', University of Florence, Florence, Italy.
⁵ Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ DEA Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁷ Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁸ Intensive Care Unit, Catholic University, Rome, Italy.
⁹ Department of Child Neurology and Psychiatry, Catholic University, Rome, Italy.
¹⁰ Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
¹¹ Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
¹² Department of Neonatal and Paediatric Intensive Care, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
¹³ Unit of Child Neuropsychiatry, University of Verona, Verona, Italy.
¹⁴ Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy.
¹⁵ Intensive Care Unit, Polytechnic University of the Marche, Ancona, Italy.
¹⁶ Intensive Care Unit, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
¹⁷ Department of Neuropsychiatry Ward, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
¹⁸ Department of Paediatric Neurology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
¹⁹ Paediatric Intensive Care Unit, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
²⁰ Department of Anaesthesia and Intensive Care, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
²¹ Paediatric Neurology Unit, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
²² Department of Paediatric Anaesthesia and Intensive Care, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
²³ Child Neuropsychiatry Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
²⁴ Research, Innovation and International Relations, Meyer Children's Hospital, Florence, Italy.
²⁵ Pharmacy Unit, Meyer Children's Hospital, Florence, Italy.

PMID: 27311915
PMCID: PMC4916612
DOI: 10.1136/bmjopen-2016-011565

Clinical Trial

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Anna Rosati et al. BMJ Open. 2016.

. 2016 Jun 15;6(6):e011565.

doi: 10.1136/bmjopen-2016-011565.

Authors

Affiliations

¹ Paediatric Neurology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
² Intensive Care Unit, Meyer Children's Hospital, Florence, Italy.
³ Clinical Trial Office Meyer Children's Hospital, Florence, Italy.
⁴ Department of Statistics, 'G Parenti', University of Florence, Florence, Italy.
⁵ Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ DEA Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁷ Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁸ Intensive Care Unit, Catholic University, Rome, Italy.
⁹ Department of Child Neurology and Psychiatry, Catholic University, Rome, Italy.
¹⁰ Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
¹¹ Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
¹² Department of Neonatal and Paediatric Intensive Care, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
¹³ Unit of Child Neuropsychiatry, University of Verona, Verona, Italy.
¹⁴ Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy.
¹⁵ Intensive Care Unit, Polytechnic University of the Marche, Ancona, Italy.
¹⁶ Intensive Care Unit, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
¹⁷ Department of Neuropsychiatry Ward, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
¹⁸ Department of Paediatric Neurology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
¹⁹ Paediatric Intensive Care Unit, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
²⁰ Department of Anaesthesia and Intensive Care, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
²¹ Paediatric Neurology Unit, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
²² Department of Paediatric Anaesthesia and Intensive Care, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
²³ Child Neuropsychiatry Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
²⁴ Research, Innovation and International Relations, Meyer Children's Hospital, Florence, Italy.
²⁵ Pharmacy Unit, Meyer Children's Hospital, Florence, Italy.

PMID: 27311915
PMCID: PMC4916612
DOI: 10.1136/bmjopen-2016-011565

Abstract

Introduction: Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE.

Methods and analysis: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method.

Ethics and dissemination: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences.

Trial registration number: NCT02431663; Pre-results.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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Figures

**Figure 1**
Flow chart. MDZ, midazolam; KE, ketamine; PR, propofol; TPS, thiopental.

See this image and copyright information in PMC

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References

1. Proposal for revised clinical and electrographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1981;22:489–501. 10.1111/j.1528-1157.1981.tb06159.x - DOI - PubMed
1. Brophy GM, Bell R, Claassen J et al. . Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012;17:3–23. 10.1007/s12028-012-9695-z - DOI - PubMed
1. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011;134:2802–18. 10.1093/brain/awr215 - DOI - PubMed
1. Raspall-Chaure M, Chin RF, Neville BG et al. . Outcome of pediatric convulsive status epilepticus: a systematic review. Lancet Neurol 2006;5:769–79. 10.1016/S1474-4422(06)70546-4 - DOI - PubMed
1. Chin RF, Neville BG, Peckham C et al. . Incidence, cause and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 2006;368:222–31. 10.1016/S0140-6736(06)69043-0 - DOI - PubMed

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Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Affiliations

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

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