Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)

September 19, 2025 updated by: Per Nordberg, Karolinska Institutet

Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)

The aim of this clinical trial is to study the impact of ultra-early transnasal evaporative cooling after cardiac arrest and subsequent hypothermia at hospital, on survival with complete neurologic recovery, compared to currently recommended normothermia. The study population will consist of patients 18-79 years old, with out-of-hospital cardiac arrest with initial shockable rhythm.

The main research question it aims to answer is whether there is a difference in survival with complete neurologic recovery at 90 days after cardiac arrest between the group of patients that received ultra-early cooling, compared to the group that was treated with normothermia.

Participants will be randomized to two groups. One group (the intervention group) will receive ultra-early trans-nasal evaporative cooling initiated by EMS personnel at the scene of the cardiac arrest, and subsequent systemic hypothermia for 24 hours at hospital arrival. The other group (the control group), will receive standard of care (advanced cardiac life support and normal body temperature (normothermia)).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1022

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA:

Patients ≥18 years that meet all of the following inclusion criteria:

  1. Adult out-of-hospital cardiac arrest patients with initial shockable rhythm
  2. Unconsciousness defined as Glasgow Coma Scale < 8
  3. Inclusion within 20 minutes from EMS arrival

EXCLUSION CRITERIA:

Patients are not eligible if they meet one or more of the following criteria:

  1. Age ≥ 80 years
  2. Obvious non-cardiac causes to cardiac arrest
  3. Obvious already hypothermic
  4. Obvious barrier to placing intra nasal catheters
  5. Have a known Do Not Attempt to Resuscitate (DNAR) order or other limitations in care
  6. Have a known terminal disease
  7. Known or clinically apparent pregnancy

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early transnasal evaporative cooling with the RhinoChill device
Early transnasal evaporative cooling initiated during ACLS at the scene of the cardiac arrest within 20 minutes from EMS arrival and subsequent hypothermia at 33ºC for 24 hours and fever control for 72 hours at the ICU
Device: Early transnasal evaporative cooling with the RhinoChill device
Early prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours
No Intervention: Standard of care
Standard advanced cardiac life support, subsequent fever control (Normothermia) for 72 hours at ICU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1.
Time Frame: Day 90
The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital
Time Frame: Day 1
Day 1
Proportion of patients alive at hospital discharge
Time Frame: Day 1-90
Day 1-90
Proportion of patients with Modified Rankin scale 0-3 at hospital discharge
Time Frame: Day 1-90
The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Day 1-90
Proportion of patients alive at 90 days
Time Frame: Day 90
Day 90
Proportion of patients with Modified Rankin scale 0-3 at 90 days
Time Frame: Day 90
The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Day 90
Device related adverse event rate within the first 24 hours
Time Frame: Day 1
Safety
Day 1
Composite serious adverse event rate within the first 7 days
Time Frame: Day 1-7
Safety
Day 1-7
Proportion of patients with new cardiac arrest prior to hospital admission
Time Frame: Day 1
Safety
Day 1

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital-free days alive at 90 days
Time Frame: Day 90
Day 90
Distribution of modified Rankin scale at 90 days
Time Frame: Day 90
The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Day 90
Distribution of Cerebral Performance Category scale at 90 days
Time Frame: Day 90
The Cerebral Performance Category (CPC) scale is a measure for neurologic function. It ranges from 1-5, where 1 equals no or minimal neurologic disabilities, and 5 equals death.
Day 90
Proportion of patients alive after 1 year
Time Frame: Day 365
Day 365
Proportion of patients with Modified Rankin scale 0-1 at 1 year
Time Frame: Day 365
The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Day 365
Quality of life assessed with EQ-5D-5L at 90 days
Time Frame: Day 90
EQ-5D is a a measure of health status and quality of life defined in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels; no problems, some or moderate problems or extreme problems.
Day 90

Collaborators and Investigators

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

Sponsor

Karolinska Institutet

Investigators

  • Principal Investigator: Per Nordberg, MD, PhD, Karolinska Institutet

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)

March 27, 2024

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

February 1, 2023

First Submitted That Met QC Criteria

September 1, 2023

First Posted (Actual)

September 6, 2023

Study Record Updates

Last Update Posted (Estimated)

September 25, 2025

Last Update Submitted That Met QC Criteria

September 19, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-02446-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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