Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada.
Dalla Lana School of Public Health, Division of Biostatistics, University of Toronto, Toronto, Canada.
Trials. 2021 Jan 6;22(1):15. doi: 10.1186/s13063-020-04946-3.
Procedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis.
METHODS/DESIGN: The Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms.
The Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes.
ClinicalTrials.gov NCT04195256 . Registered on December 11, 2019.
在为儿童进行骨折和脱位的闭合复位时，通常需要进行程序性镇静和镇痛（PSA）。静脉（IV）氯胺酮是进行闭合复位时最常用的镇静剂。然而，由于儿童认为静脉插入是一种痛苦和痛苦的程序，因此需要确定可行的替代给药途径。有证据表明，鼻内（IN）给予右美托咪定和氯胺酮（酮右旋）的组合可提供足够的镇静作用，用于闭合复位，同时避免需要静脉插入。然而，对于两种药物的最佳组合剂量以及是否可以为闭合复位提供足够的镇静作用，仍存在不确定性。鼻内右美托咪定加氯胺酮用于程序镇静（酮右旋）研究是一项在接受 PSA 进行闭合复位的儿童中进行的贝叶斯 II/III 期非劣效性试验，旨在解决这两个研究问题。本文详细介绍了酮右旋试验的统计分析计划，并在试验结果可用于分析之前提交。
方法/设计：酮右旋试验是一项多中心、四臂、随机、双盲对照、贝叶斯反应适应性剂量发现、非劣效性、II/III 期试验，旨在确定 (i) IN 酮右旋是否不劣于 IV 氯胺酮在儿科急诊室进行骨折或脱位闭合复位的儿童中进行足够的镇静作用，以及 (ii) 提供最佳镇静作用的 IN 酮右旋的组合剂量。主要使用儿科镇静状态量表来衡量足够的镇静作用。作为次要结果，酮右旋试验将比较各研究臂之间的急诊科停留时间、苏醒时间和不良事件。
酮右旋试验将提供有关 IN 酮右旋作为 IV 氯胺酮替代物的最佳剂量和有效性的证据，为接受闭合复位的患者提供镇静作用。根据本统计分析计划，将从贝叶斯角度分析酮右旋试验的数据。这将降低根据数据产生结果的风险，从而避免在我们报告的结果中引入偏差。
ClinicalTrials.gov NCT04195256。于 2019 年 12 月 11 日注册。
