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BMJ Open. 2017 Jun 21;7(6):e016031. doi: 10.1136/bmjopen-2017-016031.

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial.

Author information

1
Department of Children and Adolescents Medicine, Friedrich-Alexander-University Erlangen/Nuremberg, Erlangen, Germany.
2
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.
3
Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
4
Institute of Child Health, University College London, London, United Kingdom.
5
Therakind Ltd, London, United Kingdom.
6
UCL School of Pharmacy, University College London, London, United Kingdom.
7
Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.
8
Fondazione per la Ricerca Farmacologica Gianni Benzi onlus, Valenzano, Italy.
9
Department of Pediatric Anesthesia and Intensive Care, Astrid Lindgrens Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden.
10
Department of Pediatrics, First Faculty of Medicine, Charles University Prague, Prague, Czech Republic.
11
Clinical Trial Center, Bambino Gesù Children's Hospital, Rome, Italy.

Abstract

INTRODUCTION:

Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation.

METHODS AND ANALYSIS:

The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points.

ETHICS:

Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.

TRIAL REGISTRATION:

EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results.

KEYWORDS:

children; criticalillness; paediatrics; pharmacology; sedation

PMID:
28637741
PMCID:
PMC5726127
DOI:
10.1136/bmjopen-2017-016031
[Indexed for MEDLINE]
Free PMC Article

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