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

Antje Neubert, Manuel Alberto Baarslag, Monique Van Dijk, Joost Van Rosmalen, Joseph F. Standing, Yucheng Sheng, Wolfgang Rascher, Deborah Roberts, Jackie Winslade, Louise Rawcliffe, Sara M. Hanning, Tuuli Metsvaht, Viviana Giannuzzi, Peter Larsson, Pavla Pokorná, Alessandra Simonetti, Dick Tibboel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere016031
JournalBMJ Open
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 1 2017
Externally publishedYes

Keywords

  • children
  • criticalillness
  • paediatrics
  • pharmacology
  • sedation

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this