Prehospital Resuscitation Intra Nasal Cooling Effectiveness Survival Study (PRINCESS)

June 28, 2018 updated by: Leif Svensson, Karolinska Institutet

PRINCESS - Prehospital Resuscitation Intra Nasal Cooling Effectiveness Survival Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

700

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Department of Intensive Care, Erasme University Hospital
  • Sweden
      • Stockholm, Sweden, 11883
        • Department of Cardiology, Karolinska Institutet, Södersjukhuset

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 years
  • Collapse was witnessed (heard or seen)
  • Do not have a pulse
  • Are unresponsive to external stimuli

Exclusion Criteria:

  • Age ≥80 years
  • Have an etiology of cardiac arrest due to trauma, severe bleeding, drug overdose, cerebrovascular accident, drowning, smoke inhalation, electrocution, hanging
  • Already hypothermic (e.g., avalanche victim; found in the snow)
  • Have an obvious barrier to placing intra nasal catheters (e.g., intranasal obstruction)
  • Do Not Attempt to Resuscitate (DNAR) orders
  • Have a terminal disease
  • Known or clinically apparent pregnancy
  • Have a known coagulopathy (except therapeutically induced)
  • Are known to have a need for supplemental oxygen
  • Achieve ROSC prior to randomization
  • Response time (call to arrival) of the ambulance > 15 minutes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Patients in the control group standard advanced cardiac life support care. Patients that achieve return of spontaneous circulation will be treated with hypothermia according to current guidelines upon arrival at the intensive care unit.
Experimental: Intervention
Intra-arrest trans-nasal cooling with RhinoChill will be initiated during advanced cardiac life support. In patients achieving return of spontaneous circulation, trans-nasal cooling will continue until systemic cooling is started at the intensive care unit.
Device: Prehospital intra-nasal cooling with RhinoChill
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurologically intact survival (CPC-cerebral performance categories scale 1-2)
Time Frame: 90 days after cardiac arrest

The Cerebral Performance Categories (CPC) are used to describe neurological outcome. A CPC of 1 or 2 is considered "neurologically intact."

  1. - Good cerebral performance: little to no deficit.
  2. - Moderate cerebral disability: capable of independent activities of daily life
  3. - Severe cerebral disability: conscious, but dependent on others for daily support
  4. - Coma or vegetative state
  5. - Death or brain death
90 days after cardiac arrest

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total survival
Time Frame: 90 days
90 days
Proportion of patients achieving Return of Spontaneous Circulation (ROSC).
Time Frame: 1 hour
1 hour
Time to target temperature of 32-34º Celsius
Time Frame: 8-10 hours
8-10 hours
Admitted alive to hospital
Time Frame: 2-4 hours
Proportion of patients that are admitted alive to hospital
2-4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Karolinska University Hospital
University Hospital, Lille
Erasme University Hospital
University Hospital Hradec Kralove
CHU de Charleroi
BeneChill, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 6, 2010

Primary Completion (Actual)

January 31, 2018

Study Completion (Actual)

April 30, 2018

Study Registration Dates

First Submitted

September 9, 2010

First Submitted That Met QC Criteria

July 21, 2011

First Posted (Estimate)

July 22, 2011

Study Record Updates

Last Update Posted (Actual)

June 29, 2018

Last Update Submitted That Met QC Criteria

June 28, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRINCESS 2010/383-32

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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