TY - JOUR
T1 - The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit
T2 - Study protocol for a multicentre randomised controlled trial
AU - Neubert, Antje
AU - Baarslag, Manuel Alberto
AU - Van Dijk, Monique
AU - Van Rosmalen, Joost
AU - Standing, Joseph F.
AU - Sheng, Yucheng
AU - Rascher, Wolfgang
AU - Roberts, Deborah
AU - Winslade, Jackie
AU - Rawcliffe, Louise
AU - Hanning, Sara M.
AU - Metsvaht, Tuuli
AU - Giannuzzi, Viviana
AU - Larsson, Peter
AU - Pokorná, Pavla
AU - Simonetti, Alessandra
AU - Tibboel, Dick
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - children
KW - criticalillness
KW - paediatrics
KW - pharmacology
KW - sedation
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U2 - 10.1136/bmjopen-2017-016031
DO - 10.1136/bmjopen-2017-016031
M3 - Article
AN - SCOPUS:85021096974
VL - 7
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 6
M1 - e016031
ER -