Prehospital Resuscitation Intra Nasal Cooling Effectiveness Survival Study
Condition: Out-of-hospital Cardiac Arrest
MeSH terms: Heart Arrest; Out-of-Hospital Cardiac Arrest
Study type: Interventional
Phase: Phase 2

Summary: 
      Promising result of intra-arrest cooling on neurological intact survival in cardiac arrest
      patients has recently been published in the PRINCE-study in Circulation 2010.

      The main purpose of this study is to determine whether prehospital intra-nasal cooling
      initiated during resuscitation, in addition to systemic cooling at hospital, increases
      neurological intact survival measured as cerebral performance category score (CPC-score)at 90
      days in witnessed cardiac arrests outside hospital.
    

Detailed description: 
      Background:

      The RhinoChill Device is a non-invasive, portable cooling device through which rapid cooling
      is achieved via the trans-nasal delivery of an evaporative coolant into the nasopharynx.
      Animal studies suggest a life-saving benefit for intra-arrest cooling.

      Results from a European multicenter randomized trial (PRINCE - Pre Rosc Intra Nasal Cooling
      Effectiveness), published in Circulation in August 2010, demonstrate that intra-arrest
      trans-nasal evaporative cooling can be used safely and effectively in prehospital cardiac
      arrest without interfering with advanced cardiac life support protocols.

      The outcome results among patients admitted to hospital showed a trend towards improved
      survival to hospital discharge in the treatment group (43.8% versus 31.0, p=0.26). The
      difference in neurologically intact survival was 34.4% vs 21.4%). In the subgroup of patients
      where cardiopulmonary resuscitation (CPR) was started by Emergency Medical Services personnel
      within 10 minutes (78 % of total number of patients) the difference in total survival between
      the groups was (56.5 versus 29.4, p=0.03). Neurologically intact survival for the
      corresponding subgroup was 43.5% vs 17.6%. In the treatment group, time to tympanic
      temperature of 34º was reached 3 hours faster (102 min versus 291 min, p=0.03) and time to
      core temperature 2 hours faster (155 min versus 284 min, p=0.13).

      This study is powered to detect clinically significant changes in neurologically intact
      survival at 90 days after cardiac arrest. An interim analysis for safety and futility will be
      performed by an external committee after the first 200 patients have provided endpoint data.
      Conditional power for meeting the primary endpoint will if needed, be computed at that time,
      and if the interim results do not correspond to the primary endpoint, termination of the
      study for futility will be considered. Early stopping for efficacy reasons will only be
      considered if major outcome differences are seen between the groups according to the
      Haybittle rule with a p-value ≤0,001.

      Intention to treat and per protocol analyses will be performed for all randomized patients.
      No imputed values will be used for patients for whom data is not available.

      Stratified analyses will be performed for patients whose first recorded rhythm is VF/VT
      versus those in whom the first recorded rhythm is PEA or asystole. Stratification analyses
      will be performed for subjects where CPR was initiated within 10 minutes by a first
      responder. Stratified analyses will also be performed for subjects in the treatment group
      where cooling was started within 15 minutes.

      Besides the specific endpoints listed below, substudies will be made to assess the following
      specific endpoints:

        -  Prehospital trans-nasal cooling significantly improve the systolic left ventricular
           function measured as LVEF (performed be Echo).

        -  Prehospital trans-nasal cooling significantly reduce the infarction size and area at
           risk and increase the systolic left ventricular function measured as LVEF (ECHO and
           MRI)in patients with AMI as cause of the cardiac arrest.

        -  Prehospital trans-nasal cooling significantly reduce in-hospital MACE (Major Adverse
           Cardiac Events) (i.e. death, reinfarction, stroke, cardiogenic shock, pulmonary oedema,
           recurrent cardiac arrest and need for.IABP.during hospital stay)

        -  Prehospital trans-nasal cooling significantly reduces the proportion of patients with
           cardiogenic shock

        -  Prehospital trans-nasal cooling significantly reduce days in ventilator, days at ICU and
           length of stay at hospital among survivors.

        -  To perform a metaanalysis in regards to ROSC, early and late survival as a pooled
           analysis of PRINCE data and PRINCESS 200 patientdata.

        -  Prehospital trans-nasal cooling significantly reduces peak-value of biochemical markers
           in patients treated with RhinoChill with 25% (measured at 12, 24, 36, 48 and 72 hours).

        -  To assess the development of end tidal CO2 during resuscitation in patients cooled
           prehospital wit trans nasal cooling
    

Intervention name(s): Prehospital intra-nasal cooling with RhinoChill
Intervention type(s): Device
Intervention description(s): Patients in the intervention group will receive prehospital intra-nasal cooling with RhinoChill as soon as possible during the resuscitation (i.e. intra-arrest). Intra-nasal cooling will be ongoing until systemic hypothermia is started at the intensive care unit.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypothermia, induced; Intra-arrest cooling; Cardiac arrest; Prehospital emergency care; Emergency Medical Services