Neubert Antje, Baarslag Manuel Alberto, Dijk Monique van, Rosmalen Joost van, Standing Joseph F, Sheng Yucheng, Rascher Wolfgang, Roberts Deborah, Winslade Jackie, Rawcliffe Louise, Hanning Sara M, Metsvaht Tuuli, Giannuzzi Viviana, Larsson Peter, Pokorná Pavla, Simonetti Alessandra, Tibboel Dick
Department of Children and Adolescents Medicine, Friedrich-Alexander-University Erlangen/Nuremberg, Erlangen, Germany.
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.
BMJ Open. 2017 Jun 21;7(6):e016031. doi: 10.1136/bmjopen-2017-016031.
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.
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.
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.
EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results.
镇静是儿科重症监护的重要组成部分。咪达唑仑通常与阿片类药物联合使用，是目前的金标准药物。然而，由于它远非理想药物，可乐定在儿童中的使用越来越多。与儿科的许多药物一样，这种药物针对该适应症的使用属于超说明书用药。因此，CLOSED试验旨在提供可乐定用于机械通气患者镇静的药代动力学、安全性和有效性数据，以获得儿科用药上市许可。
CLOSED研究是一项多中心、双盲、随机、活性对照的非劣效性试验，可乐定与咪达唑仑按1:1随机分组。两个治疗组均按年龄分为三个规模相同的组：<28天（n = 100）、28天至<2岁（n = 100）和2 - 18岁（n = 100）。主要终点定义为研究期间镇静失败的发生情况。次要终点包括药代动力学/药效学关系、药物遗传学、谵妄和戒断综合征的发生情况、阿片类药物消耗量以及新生儿年龄组的神经发育情况。主要终点将采用逻辑回归分析，次要终点将采用适当的统计学方法。
将从父母/照料者处获得书面知情同意书。在国家立法允许的地点将采用口头或延迟同意。该研究已获得各招募地点机构审查委员会的批准。研究结果将发表在同行评审期刊上，并与全球医学界共享。
欧洲临床试验数据库：2014 - 003582 - 24；美国国立医学图书馆临床试验注册库：NCT02509273；预结果。
