Heath Anna, Yaskina Maryna, Hopkin Gareth, Klassen Terry P, McCabe Christopher, Offringa Martin, Pechlivanoglou Petros, Rios Juan David, Poonai Naveen, Ali Samina
Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Trials. 2020 Sep 3;21(1):759. doi: 10.1186/s13063-020-04503-y.
Pediatric musculoskeletal injuries cause moderate to severe pain, which should ideally be addressed upon arrival to the emergency department (ED). Despite extensive research in ED-based pediatric pain treatment, recent studies confirm that pain management in this setting remains suboptimal. The No OUCH study consist of two complementary, randomized, placebo-controlled trials that will run simultaneously for patients presenting to the ED with an acute limb injury and a self-reported pain score of at least 5/10, measured via a verbal numerical rating scale (vNRS). Caregiver/parent choice will determine whether patients are randomized to the two-arm or three-arm trial. In the two-arm trial, patients will be randomized to receive either ibuprofen alone or ibuprofen in combination with acetaminophen. In the three-arm trial, patients can also be randomized to a third arm where they would receive ibuprofen in combination with hydromorphone. This article details the statistical analysis plan for the No OUCH study and was submitted before the trial outcomes were available for analysis.
METHODS/DESIGN: The primary endpoint of the No OUCH study is self-reported pain at 60 min, recorded using a vNRS. The principal safety outcome is the presence of any adverse event related to study drug administration. Secondary effectiveness endpoints include pain measurements using the Faces Pain Scale-Revised and the visual analog scale, time to effective analgesia, requirement of a rescue analgesic, missed fractures, and observed pain reduction using different definitions of successful analgesia. Secondary safety outcomes include sedation measured using the Ramsay Sedation Score and serious adverse events. Finally, the No OUCH study investigates the reasons given by the caregiver for selecting the two-arm (Non-Opioid) or three-arm (Opioid) trial, caregiver satisfaction, physician preferences for analgesics, and caregiver comfort with at-home pain management.
The No OUCH study will inform the relative effectiveness of acetaminophen and hydromorphone, in combination with ibuprofen, and ibuprofen alone as analgesic agents for patients presenting to the ED with an acute musculoskeletal injury. The data from these trials will be analyzed in accordance with this statistical analysis plan. This will reduce the risk of producing data-driven results and bias in our reported outcomes.
ClinicalTrials.gov NCT03767933 . Registered on December 7, 2018.
小儿肌肉骨骼损伤会导致中度至重度疼痛，理想情况下应在抵达急诊科（ED）时进行处理。尽管在基于急诊科的小儿疼痛治疗方面进行了广泛研究，但最近的研究证实，这种情况下的疼痛管理仍未达到最佳水平。“无疼痛”（No OUCH）研究包括两项互补的随机、安慰剂对照试验，将同时针对因急性肢体损伤到急诊科就诊且通过口头数字评定量表（vNRS）自我报告疼痛评分至少为5/10的患者进行。照顾者/家长的选择将决定患者被随机分配到双臂试验还是三臂试验。在双臂试验中，患者将被随机分配接受单独使用布洛芬或布洛芬与对乙酰氨基酚联合使用。在三臂试验中，患者也可被随机分配到第三组，接受布洛芬与氢吗啡酮联合使用。本文详细介绍了“无疼痛”研究的统计分析计划，该计划在试验结果可供分析之前提交。
方法/设计：“无疼痛”研究的主要终点是使用vNRS记录的60分钟时的自我报告疼痛。主要安全结局是与研究药物给药相关的任何不良事件的发生情况。次要有效性终点包括使用面部疼痛量表修订版和视觉模拟量表进行的疼痛测量、有效镇痛时间、急救镇痛药的需求、漏诊骨折以及使用不同成功镇痛定义观察到的疼痛减轻情况。次要安全结局包括使用拉姆齐镇静评分测量的镇静情况和严重不良事件。最后，“无疼痛”研究调查照顾者选择双臂（非阿片类）或三臂（阿片类）试验的原因、照顾者满意度、医生对镇痛药的偏好以及照顾者对家庭疼痛管理的舒适度。
“无疼痛”研究将为对乙酰氨基酚和氢吗啡酮与布洛芬联合使用以及单独使用布洛芬作为因急性肌肉骨骼损伤到急诊科就诊患者的镇痛药的相对有效性提供信息。这些试验的数据将根据此统计分析计划进行分析。这将降低产生数据驱动结果和报告结果偏差的风险。
ClinicalTrials.gov NCT03767933。于2018年12月7日注册。
