PRINCESS2: Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2

Sponsor

Karolinska Institutet (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06025123

Collaborator

(none)

970

Enrollment

Locations

Arms

Anticipated Duration (Months)

194

Patients Per Site

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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)).

Condition or Disease	Intervention/Treatment	Phase
Out-Of-Hospital Cardiac Arrest Hypothermia Ventricular Fibrillation	Device: Early transnasal evaporative cooling with the RhinoChill device	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

970 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Investigator, Outcomes Assessor)

Masking Description:

Patients in the intervention group will be treated with hypothermia, which makes blinding for care provider and next of kin difficult in the intervention phase (first 36 h). Participants will be informed of which group the were assigned to if they regained consciousness. The study personnel assessing neurologic outcome at discharge and at 90 days will be blinded for which study group the participant belongs to. In addition, the physician performing the prognostication at 72 hours from cardiac arrest will be a neurologist, intensivist or other specialist experienced and will be blinded for group allocation, but not for relevant clinical data.

Primary Purpose:

Treatment

Official Title:

Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1. [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.

Secondary Outcome Measures

Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital [Day 1]
Proportion of patients alive at hospital discharge [Day 1-90]
Proportion of patients with Modified Rankin scale 0-3 at hospital discharge [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.
Proportion of patients alive at 90 days [Day 90]
Proportion of patients with Modified Rankin scale 0-3 at 90 days [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.
Device related adverse event rate within the first 24 hours [Day 1]
Safety
Composite serious adverse event rate within the first 7 days [Day 1-7]
Safety
Proportion of patients with new cardiac arrest prior to hospital admission [Day 1]
Safety

Other Outcome Measures

Hospital-free days alive at 90 days [Day 90]
Distribution of modified Rankin scale at 90 days [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.
Distribution of Cerebral Performance Category scale at 90 days [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.
Proportion of patients alive after 1 year [Day 365]
Proportion of patients with Modified Rankin scale 0-1 at 1 year [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.
Quality of life assessed with EQ-5D-5L at 90 days [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

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

EXCLUSION CRITERIA:

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

Contacts and Locations

Locations

	Site	City	Country
1	University Hospital Vienna	Vienna	Austria
2	Erasme University Hospital	Brussels	Belgium
3	Charles University of Prague	Prague	Czechia
4	University Hospital Freiburg	Freiburg	Germany
5	Ljubljana University Medical Centre	Ljubljana	Slovenia