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).
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.



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.



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.



NCT02431663; Pre-results.
Paediatric Neurology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
Anna
A
Rosati
Paediatric Neurology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
Lucrezia
L
Ilvento
Intensive Care Unit, Meyer Children's Hospital, Florence, Italy.
Manuela
M
L'Erario
Clinical Trial Office Meyer Children's Hospital, Florence, Italy.
Salvatore
S
De Masi
Department of Statistics, 'G Parenti', University of Florence, Florence, Italy.
Annibale
A
Biggeri
Department of Statistics, 'G Parenti', University of Florence, Florence, Italy.
Giancarlo
G
Fabbro
Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Roberto
R
Bianchi
DEA Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Francesca
F
Stoppa
Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Lucia
L
Fusco
Intensive Care Unit, Catholic University, Rome, Italy.
Silvia
S
Pulitanò
Department of Child Neurology and Psychiatry, Catholic University, Rome, Italy.
Domenica
D
Battaglia
Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
Andrea
A
Pettenazzo
Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy.
Stefano
S
Sartori
Department of Neonatal and Paediatric Intensive Care, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Paolo
P
Biban
Unit of Child Neuropsychiatry, University of Verona, Verona, Italy.
Elena
E
Fontana
Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy.
Elisabetta
E
Cesaroni
Intensive Care Unit, Polytechnic University of the Marche, Ancona, Italy.
Donatella
D
Mora
Intensive Care Unit, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
Paola
P
Costa
Department of Neuropsychiatry Ward, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
Rosanna
R
Meleleo
Department of Paediatric Neurology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
Roberta
R
Vittorini
Paediatric Intensive Care Unit, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
Alessandra
A
Conio
Department of Anaesthesia and Intensive Care, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
Andrea
A
Wolfler
Paediatric Neurology Unit, Women and Children's Hospital Vittore Buzzi, ICP, Milan, Italy.
Massimo
M
Mastrangelo
Department of Paediatric Anaesthesia and Intensive Care, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Maria Cristina
MC
Mondardini
Child Neuropsychiatry Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Emilio
E
Franzoni
Research, Innovation and International Relations, Meyer Children's Hospital, Florence, Italy.
Kathleen S
KS
McGreevy
Pharmacy Unit, Meyer Children's Hospital, Florence, Italy.
Lorena
L
Di Simone
Clinical Trial Office Meyer Children's Hospital, Florence, Italy.
Alessandra
A
Pugi
Intensive Care Unit, Meyer Children's Hospital, Florence, Italy.
Lorenzo
L
Mirabile
Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Federico
F
Vigevano
Paediatric Neurology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
Renzo
R
Guerrini
D061605:Administration, Intravenous; D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D012107:Research Design; D013226:Status Epilepticus / Q000188:drug therapy*; D016896:Treatment Outcome
D000927:Anticonvulsants; D007649:Ketamine