Abstract 151: The PRINCESS 2 Trial: A Randomized Study to Assess the Impact of Ultrafast Hypothermia on Neurologic Function in Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm

Abstract

Background: The impact 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 transnasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature. 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. Methods/Design: This investigator-initiated, randomized, controlled trial will randomize patients at the scene of cardiac arrest to either transnasal cooling within 20 minutes from Emergency Medical System 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 o 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, 970 patients are required to detect an absolute difference of 9 % (from 45 to 54 %) in survival with neurologic recovery (80 % power and 2-sided α=0,5). Recruitment starts in Q3 2023 and we expect maximum enrolment to be achieved during 2024 at 20-25 European and US sites. Discussion: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest on survival with complete neurologic recovery in patients with OHCA and shockable rhythm