Abstract：
Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms.
In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, β=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites.
This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm.
NCT06025123.
In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, β=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites.
This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm.
NCT06025123.
摘要：
背景：延迟低温，在医院到达后开始，心脏骤停几小时后8-10小时达到目标温度，可能对总体生存率的影响有限。然而,超快低温的影响，即停搏内或自主循环(ROSC)恢复后立即交付，院外心脏骤停(OHCA)后的神经功能结局尚不清楚.在之前的两次审判中，院前经鼻蒸发停止冷却是安全的，与延迟冷却相比，可行且缩短了达到目标温度的时间。两项研究都显示了具有可电击节律的患者神经系统恢复改善的趋势。PRINCESS2研究的目的是评估是否冷却，在ROSC内部或之后立即启动，随后是住院期间的体温过低,与标准的正常体温治疗相比，在神经系统完全恢复的情况下显着增加了生存率，OHCA患者具有可电击节律。
方法：在这个研究者发起的，随机化，对照试验,急诊医疗服务（EMS）将患者在心搏骤停现场随机分配，在EMS到达后20分钟内接受经鼻降温，随后在33°C下进行低温治疗24小时入院（干预），或没有院前或院内冷却的护理标准（对照）。在前72小时内，两组均可避免发烧（>37,7°C）。所有患者都将接受复苏后护理，并根据当前指南退出生命支持程序。主要结果是在90天时神经系统完全恢复的存活，定义为改良的兰金量表(mRS)0-1。关键的次要结果包括生存到出院，90天的存活率和90天的mRS0-3。总的来说,1022名患者需要检测到9％（从45％到54％）的绝对差异，在神经系统恢复（80％的功率和单侧α=0,025，β=0,2）和假设2,5％的损失随访。招聘将于2024年第一季度开始，我们预计2024年第四季度将在20-25个欧洲和美国站点实现最大入学率。
结论：本试验将评估超快低温对心脏骤停的影响，与正常体温相比，在OHCA患者的90天生存和完全的神经系统恢复初始电击心律。
背景：NCT06025123。
方法：在这个研究者发起的，随机化，对照试验,急诊医疗服务（EMS）将患者在心搏骤停现场随机分配，在EMS到达后20分钟内接受经鼻降温，随后在33°C下进行低温治疗24小时入院（干预），或没有院前或院内冷却的护理标准（对照）。在前72小时内，两组均可避免发烧（>37,7°C）。所有患者都将接受复苏后护理，并根据当前指南退出生命支持程序。主要结果是在90天时神经系统完全恢复的存活，定义为改良的兰金量表(mRS)0-1。关键的次要结果包括生存到出院，90天的存活率和90天的mRS0-3。总的来说,1022名患者需要检测到9％（从45％到54％）的绝对差异，在神经系统恢复（80％的功率和单侧α=0,025，β=0,2）和假设2,5％的损失随访。招聘将于2024年第一季度开始，我们预计2024年第四季度将在20-25个欧洲和美国站点实现最大入学率。
结论：本试验将评估超快低温对心脏骤停的影响，与正常体温相比，在OHCA患者的90天生存和完全的神经系统恢复初始电击心律。
背景：NCT06025123。
