Out-Of-Hospital Cardiac ArrestPRINCESS2NCT06025123
Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2
A study testing Early transnasal evaporative cooling with the RhinoChill device in people with Out-Of-Hospital Cardiac Arrest and Hypothermia, run by Karolinska Institutet at 17 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Out-Of-Hospital Cardiac Arrest, Hypothermia, Ventricular Fibrillation
- What is being tested?
- Early transnasal evaporative cooling with the RhinoChill device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,022 participants
- Where
- 17 sitesin 8 countries
- Study dates
- 27 Mar 2024to May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years that meet all of the following inclusion criteria:
- Adult out-of-hospital cardiac arrest patients with initial shockable rhythm
- Unconsciousness defined as Glasgow Coma Scale < 8
- Inclusion within 20 minutes from EMS arrival
Who cannot join
- Patients are not eligible if they meet one or more of the following criteria:
- Age ≥ 80 years
- Obvious non-cardiac causes to cardiac arrest
- Obvious already hypothermic
- Obvious barrier to placing intra nasal catheters
- Have a known Do Not Attempt to Resuscitate (DNAR) order or other limitations in care
- Have a known terminal disease
- Known or clinically apparent pregnancy
Trial locations and contacts
17 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
17 sites in 8 countries
Germany5 sites, 5 recruiting
- Not yet recruiting
Klinikum Bamberg (Sozialstiftung Bamberg).
Bamberg
Lukas Tadda, Lukas.Tadda@sozialstiftung-bamberg.de
- Recruiting
University Hospital Freiburg
Freiburg im Breisgau
Hans-Jörg Busch, MD, PhD, hans-joerg.busch@uniklinik-freiburg.de
- Recruiting
Christliches Klinikum Halle
Halle
Harald Fritz, harald.fritz@martha-maria.de
Antje Patzig, a.patzig@ck-halle.de
- Recruiting
Universitätsklinikum Halle
Halle
Jörn Tongers, joern.tongers@uk-halle.de
- Recruiting
Asklepios Südpfalzklinik
Kandel
Manuel Ligner, m.lingner@asklepios.com
Belgium3 sites, 3 recruiting
- Recruiting
CHU Saint-Pierre
Brussels
Marie-Astrid de Villenfagne, PhD, marie-astrid.devillenfagne@stpierre-bru.be
- Recruiting
Erasme University Hospital
Brussels
Fabio S Taccone, MD, PhD, fabio.taccone@ulb.be
- Recruiting
Europe Hospitals St Elizabeth
Brussels
Michael Vandoorslaert, PhD, M.VANDOORSLAERT@europehospitals.be
Austria2 sites, 2 recruiting
- Recruiting
Medizinische Universität Graz, Abteilung für Kardiologie
Graz
Dirk von Lewinski, dirk.von-lewinski@medunigraz.at
- Recruiting
University Hospital Vienna
Vienna
Michael Holzer, MD, PhD, michael.holzer@meduniwien.ac.at
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitario La Paz
Madrid
Sandra O Rosillo Rodríguez, PhD, sorrph17@gmail.com
Ervigio Corral Torres, corralte@madrid.es
- Recruiting
San Carlos Clinical Hospital
Madrid
Miguel Sanchez, PhD
Juan Carlos Martín Benítez, PhD
Sweden2 sites, 2 recruiting
- Recruiting
Karolinska University Hospital
Stockholm
Per Nordberg, PhD, per.nordberg@ki.se
- Recruiting
Södersjukhuset
Stockholm
Emelie Dillenbeck, MD, emelie.dillenbeck@ki.se
Akil Awad, PhD, akil.awad@ki.se
Italy1 site, 1 recruiting
- Not yet recruiting
Department of Anesthesiology, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
Giuseppe Ristagno, Prof, gristag@gmail.com
Norway1 site, 1 recruiting
- Recruiting
Ullevål hospital
Oslo
Kristin Alm-Kruse, kellings@ous-hf.no
Slovenia1 site, 1 recruiting
- Recruiting
Ljubljana University Medical Centre
Ljubljana
Peter Radsel, MD, pradsel@gmail.com
About this study
Official title: 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)).
- Being tested
- Early transnasal evaporative cooling with the RhinoChill device
- Keywords
- Therapeutic hypothermia, transnasal cooling, neurologic outcome, ultrafast hypothermia, prehospital, ECPR
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Hypothermia, Ventricular Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early transnasal evaporative cooling with the RhinoChill deviceDevice
Early prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours
| Study group | Role | What they receive |
|---|---|---|
| Early transnasal evaporative cooling with the RhinoChill device | Experimental | 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 Receives: Device: Early transnasal evaporative cooling with the RhinoChill device |
| Standard of care | No intervention | Standard advanced cardiac life support, subsequent fever control (Normothermia) for 72 hours at ICU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1.
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.
Measured: Day 90
Secondary outcomes (8)
Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital
Measured: Day 1
Proportion of patients alive at hospital discharge
Measured: Day 1-90
Proportion of patients with Modified Rankin scale 0-3 at hospital discharge
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.
Measured: Day 1-90
Proportion of patients alive at 90 days
Measured: Day 90
Proportion of patients with Modified Rankin scale 0-3 at 90 days
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.
Measured: Day 90
Device related adverse event rate within the first 24 hours
Safety
Measured: Day 1
Composite serious adverse event rate within the first 7 days
Safety
Measured: Day 1-7
Proportion of patients with new cardiac arrest prior to hospital admission
Safety
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2023
- Study start27 Mar 2024
- Primary completionFeb 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Out-Of-Hospital Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized by EMS personnel at the scene of cardiac arrest to either a) intervention: early transnasal evaporative cooling initiated within 20 minutes from EMS arrival, and subsequent systemic hypothermia at 33°C for 24 h and fever control for 72 h in the ICU, or b) control: standard ACLS (advanced cardiac life support) and fever control (normothermia) for 72 h in the ICU.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 1,022 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Per Nordberg, Karolinska Institutet
- Investigators
- Per Nordberg, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06025123
- Sponsor's protocol ID
- 2022-02446-01
- Acronym
- PRINCESS2
- Status last verified
- Sep 2025
- First submitted
- 1 Feb 2023
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dillenbeck E, Berthelsen T, Corral Torres E, Lopez-de-Sa E, Rosillo Rodriguez SO, Sanchez-Garcia M, Martin Benitez JC, Busch HJ, Radsel P, Ristagno G, Nichol G, Holzer M, Moreau A, Forsberg S, Backstrom D, Awad A, Taccone FS, Falk A, Hollenberg J, Jonsson M, Liliequist A, Jurga J, Okas M, Svensson L, Nordberg P. On-scene selective brain cooling in ventricular fibrillation cardiac arrest: pilot results from the PRINCESS2 randomised trial. Crit Care. 2026 Feb 12;30(1):93. doi: 10.1186/s13054-026-05851-y.
PubMed 41680915Dillenbeck E, Hollenberg J, Holzer M, Busch HJ, Nichol G, Radsel P, Belohlavec J, Torres EC, Lopez-de-Sa E, Rosell F, Ristagno G, Forsberg S, Annoni F, Svensson L, Jonsson M, Backstrom D, Gellerfors M, Awad A, Taccone FS, Nordberg P. The design of the PRINCESS 2 trial: A randomized trial to study the impact of ultrafast hypothermia on complete neurologic recovery after out-of-hospital cardiac arrest with initial shockable rhythm. Am Heart J. 2024 May;271:97-108. doi: 10.1016/j.ahj.2024.02.020. Epub 2024 Feb 28.
PubMed 38417773
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)
- ClinicalTrials.gov ID
- NCT06025123
- Acronym / sponsor ID
- PRINCESS2 / 2022-02446-01
- Keywords
- Therapeutic hypothermia, transnasal cooling, neurologic outcome, ultrafast hypothermia, prehospital, ECPR
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,022 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- 27 Mar 2024 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 6 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized by EMS personnel at the scene of cardiac arrest to either a) intervention: early transnasal evaporative cooling initiated within 20 minutes from EMS arrival, and subsequent systemic hypothermia at 33°C for 24 h and fever control for 72 h in the ICU, or b) control: standard ACLS (advanced cardiac life support) and fever control (normothermia) for 72 h in the ICU.
| Arm | Type | Receives |
|---|---|---|
| Early transnasal evaporative cooling with the RhinoChill device | Experimental | Device: Early transnasal evaporative cooling with the RhinoChill deviceEarly 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 |
| Standard of care | No intervention | –Standard advanced cardiac life support, subsequent fever control (Normothermia) for 72 hours at ICU |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult out-of-hospital cardiac arrest patients with initial shockable rhythm
- Unconsciousness defined as Glasgow Coma Scale < 8
- Inclusion within 20 minutes from EMS arrival
Key exclusion criteria (8 listed)
- Age ≥ 80 years
- Obvious non-cardiac causes to cardiac arrest
- Obvious already hypothermic
- Obvious barrier to placing intra nasal catheters
- Have a known Do Not Attempt to Resuscitate (DNAR) order or other limitations in care
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early transnasal evaporative cooling with the RhinoChill deviceEarly prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours | Device | Early transnasal evaporative cooling with the RhinoChill device |
Primary outcome
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.
8 secondary outcomes
Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital
Time frame: Day 1
Proportion of patients alive at hospital discharge
Time frame: Day 1-90
Proportion of patients with Modified Rankin scale 0-3 at hospital discharge
Time frame: Day 1-90
Proportion of patients alive at 90 days
Time frame: Day 90
Proportion of patients with Modified Rankin scale 0-3 at 90 days
Time frame: Day 90
Device related adverse event rate within the first 24 hours
Time frame: Day 1
Composite serious adverse event rate within the first 7 days
Time frame: Day 1-7
Proportion of patients with new cardiac arrest prior to hospital admission
Time frame: Day 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Derived from this study: PubMed 41680915Dillenbeck E, Berthelsen T, Corral Torres E, Lopez-de-Sa E, Rosillo Rodriguez SO, Sanchez-Garcia M, Martin Benitez JC, Busch HJ, Radsel P, Ristagno G, Nichol G, Holzer M, Moreau A, Forsberg S, Backstrom D, Awad A, Taccone FS, Falk A, Hollenberg J, Jonsson M, Liliequist A, Jurga J, Okas M, Svensson L, Nordberg P. On-scene selective brain cooling in ventricular fibrillation cardiac arrest: pilot results from the PRINCESS2 randomised trial. Crit Care. 2026 Feb 12;30(1):93. doi: 10.1186/s13054-026-05851-y.
- Derived from this study: PubMed 38417773Dillenbeck E, Hollenberg J, Holzer M, Busch HJ, Nichol G, Radsel P, Belohlavec J, Torres EC, Lopez-de-Sa E, Rosell F, Ristagno G, Forsberg S, Annoni F, Svensson L, Jonsson M, Backstrom D, Gellerfors M, Awad A, Taccone FS, Nordberg P. The design of the PRINCESS 2 trial: A randomized trial to study the impact of ultrafast hypothermia on complete neurologic recovery after out-of-hospital cardiac arrest with initial shockable rhythm. Am Heart J. 2024 May;271:97-108. doi: 10.1016/j.ahj.2024.02.020. Epub 2024 Feb 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Per Nordberg, MD, PhD principal investigator
Karolinska Institutet
17 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early transnasal evaporative cooling with the RhinoChill device in people with Out-Of-Hospital Cardiac Arrest and Hypothermia, run by Karolinska Institutet at 17 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Germany, Belgium, Austria, Spain, Sweden and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Per Nordberg, MD, PhD (+46702802579, per.nordberg@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1. (time frame: Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06025123, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.