de Grunt Midas N, Risvanoglu Nurseda, Siegers Johannes A, Kroon Maurice A G M, Merkus Maruschka P, Hollmann Markus W, Ridderikhof Milan L, Weenink Robert P
Amsterdam UMC, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Ambulance Amsterdam, Karperweg 19-25, Amsterdam, 1075 LB, The Netherlands.
Trials. 2025 May 26;26(1):172. doi: 10.1186/s13063-025-08869-9.
Although fentanyl and esketamine, administered intravenously (IV) or intranasally (IN), are standard of care for treatment of acute traumatic pain in the prehospital setting in the Netherlands, comparative evidence regarding their efficacy and safety is lacking. Therefore, this study aims to assess the efficacy and safety of fentanyl IN, esketamine IV and esketamine IN as compared to fentanyl IV for management of acute traumatic pain in the prehospital setting.
This is a double-blind, monocenter, multi-arm, randomized non-inferiority trial in the prehospital setting in the Netherlands. Adult subjects receiving emergency care from Emergency Medical Services Ambulance Amsterdam and suffering from acute severe traumatic pain are randomized in an 1:1:1:1 ratio to receive fentanyl IV (1.0 µg/kg), fentanyl IN (1.25 µg/kg), esketamine IV (0.2 mg/kg), or esketamine IN (0.625 mg/kg). The primary endpoint is the reduction in Numeric Rating Scale (NRS, 0-10) score at 10 min after first administration of study medication. The prespecified non-inferiority margin is 1.0 for the between-group absolute difference in primary outcome. The primary endpoint is analyzed according to the intention-to-treat and per-protocol principles conforming to recommendations for non-inferiority analysis. Other endpoints include reduction in NRS score at other timepoints, need for additional analgesia, patient satisfaction, and adverse events.
This trial is one of few double-blind randomized controlled trials in the prehospital setting and aims to answer questions that have relevance to prehospital practice. Research in a prehospital emergency setting also comes with challenges, including concerns about prehospital data quality, limited research experience among personnel and a limited timeframe for data collection and follow-up. Also, informed consent needs to be deferred.
ClinicalTrials.gov NCT06051227. Registered on 9 September 2023.
尽管静脉注射（IV）或鼻内给药（IN）的芬太尼和艾司氯胺酮是荷兰院前环境中治疗急性创伤性疼痛的标准治疗方法，但关于它们疗效和安全性的比较证据尚缺。因此，本研究旨在评估与静脉注射芬太尼相比，鼻内给予芬太尼、静脉注射艾司氯胺酮和鼻内给予艾司氯胺酮在院前环境中治疗急性创伤性疼痛的疗效和安全性。
这是一项在荷兰院前环境中进行的双盲、单中心、多臂、随机非劣效性试验。从阿姆斯特丹紧急医疗服务救护车接受紧急护理且患有急性重度创伤性疼痛的成年受试者按1:1:1:1的比例随机分组，分别接受静脉注射芬太尼（1.0μg/kg）、鼻内给予芬太尼（1.25μg/kg）、静脉注射艾司氯胺酮（0.2mg/kg）或鼻内给予艾司氯胺酮（0.625mg/kg）。主要终点是首次给予研究药物后10分钟时数字评定量表（NRS，0 - 10）评分的降低。预设的非劣效性界值为主要结局组间绝对差异1.0。主要终点根据意向性分析和符合非劣效性分析建议的符合方案原则进行分析。其他终点包括其他时间点NRS评分的降低、额外镇痛的需求、患者满意度和不良事件。
本试验是院前环境中为数不多的双盲随机对照试验之一，旨在回答与院前实践相关的问题。院前紧急环境中的研究也面临挑战，包括对院前数据质量的担忧、人员研究经验有限以及数据收集和随访的时间框架有限。此外，需要推迟获得知情同意。
ClinicalTrials.gov NCT06051227。于2023年9月9日注册。
