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).

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.

• Authors: Anna Rosati, Lucrezia Ilvento, Manuela L'Erario, Salvatore De Masi, Annibale Biggeri, Giancarlo Fabbro, Roberto Bianchi, Francesca Stoppa, Lucia Fusco, Silvia Pulitanò, Domenica Battaglia, Andrea Pettenazzo, Stefano Sartori, Paolo Biban, Elena Fontana, Elisabetta Cesaroni, Donatella Mora, Paola Costa, Rosanna Meleleo, Roberta Vittorini, Alessandra Conio, Andrea Wolfler, Massimo Mastrangelo, Maria Cristina Mondardini, Emilio Franzoni, Kathleen S McGreevy, Lorena Di Simone, Alessandra Pugi, Lorenzo Mirabile, Federico Vigevano, Renzo Guerrini
• Journal: BMJ open (BMJ Open) Vol. 6 Issue 6 Pg. e011565 (06 15 2016) ISSN: 2044-6055 [Electronic] England
• PMID: 27311915 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 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/

Chemical References

• Anticonvulsants
• Ketamine

Topics

• Administration, Intravenous
• Adolescent
• Anticonvulsants (administration & dosage)
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Italy
• Ketamine (administration & dosage)
• Male
• Research Design
• Status Epilepticus (drug therapy)
• Treatment Outcome