xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06025123</url>
    </required_header>
    <id_info>
      <org_study_id>2022-02446-01</org_study_id>
      <nct_id>NCT06025123</nct_id>
    </id_info>
    <brief_title>Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2</brief_title>
    <acronym>PRINCESS2</acronym>
    <official_title>Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Karolinska Institutet</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Karolinska Institutet</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this clinical trial is to study the impact of ultra-early transnasal evaporative&#xD;
        cooling after cardiac arrest and subsequent hypothermia at hospital, on survival with&#xD;
        complete neurologic recovery, compared to currently recommended normothermia. The study&#xD;
        population will consist of patients 18-79 years old, with out-of-hospital cardiac arrest with&#xD;
        initial shockable rhythm.&#xD;
  &#xD;
        The main research question it aims to answer is whether there is a difference in survival&#xD;
        with complete neurologic recovery at 90 days after cardiac arrest between the group of&#xD;
        patients that received ultra-early cooling, compared to the group that was treated with&#xD;
        normothermia.&#xD;
  &#xD;
        Participants will be randomized to two groups. One group (the intervention group) will&#xD;
        receive ultra-early trans-nasal evaporative cooling initiated by EMS personnel at the scene&#xD;
        of the cardiac arrest, and subsequent systemic hypothermia for 24 hours at hospital arrival.&#xD;
        The other group (the control group), will receive standard of care (advanced cardiac life&#xD;
        support and normal body temperature (normothermia)).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">March 2027</completion_date>
    <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <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.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Investigator, Outcomes Assessor)</masking>
      <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.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1.</measure>
      <time_frame>Day 90</time_frame>
      <description>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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital</measure>
      <time_frame>Day 1</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients alive at hospital discharge</measure>
      <time_frame>Day 1-90</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients with Modified Rankin scale 0-3 at hospital discharge</measure>
      <time_frame>Day 1-90</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients alive at 90 days</measure>
      <time_frame>Day 90</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients with Modified Rankin scale 0-3 at 90 days</measure>
      <time_frame>Day 90</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Device related adverse event rate within the first 24 hours</measure>
      <time_frame>Day 1</time_frame>
      <description>Safety</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite serious adverse event rate within the first 7 days</measure>
      <time_frame>Day 1-7</time_frame>
      <description>Safety</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients with new cardiac arrest prior to hospital admission</measure>
      <time_frame>Day 1</time_frame>
      <description>Safety</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Hospital-free days alive at 90 days</measure>
      <time_frame>Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Distribution of modified Rankin scale at 90 days</measure>
      <time_frame>Day 90</time_frame>
      <description>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.</description>
    </other_outcome>
    <other_outcome>
      <measure>Distribution of Cerebral Performance Category scale at 90 days</measure>
      <time_frame>Day 90</time_frame>
      <description>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.</description>
    </other_outcome>
    <other_outcome>
      <measure>Proportion of patients alive after 1 year</measure>
      <time_frame>Day 365</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion of patients with Modified Rankin scale 0-1 at 1 year</measure>
      <time_frame>Day 365</time_frame>
      <description>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.</description>
    </other_outcome>
    <other_outcome>
      <measure>Quality of life assessed with EQ-5D-5L at 90 days</measure>
      <time_frame>Day 90</time_frame>
      <description>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.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">970</enrollment>
    <condition>Out-Of-Hospital Cardiac Arrest</condition>
    <condition>Hypothermia</condition>
    <condition>Ventricular Fibrillation</condition>
    <arm_group>
      <arm_group_label>Early transnasal evaporative cooling with the RhinoChill device</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard of care</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Standard advanced cardiac life support, subsequent fever control (Normothermia) for 72 hours at ICU</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Early transnasal evaporative cooling with the RhinoChill device</intervention_name>
      <description>Early prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours</description>
      <arm_group_label>Early transnasal evaporative cooling with the RhinoChill device</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          INCLUSION CRITERIA:&#xD;
  &#xD;
          Patients ≥18 years that meet all of the following inclusion criteria:&#xD;
  &#xD;
            1. Adult out-of-hospital cardiac arrest patients with initial shockable rhythm&#xD;
  &#xD;
            2. Unconsciousness defined as Glasgow Coma Scale &lt; 8&#xD;
  &#xD;
            3. Inclusion within 20 minutes from EMS arrival&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
          Patients are not eligible if they meet one or more of the following criteria:&#xD;
  &#xD;
            1. Age ≥ 80 years&#xD;
  &#xD;
            2. Obvious non-cardiac causes to cardiac arrest&#xD;
  &#xD;
            3. Obvious already hypothermic&#xD;
  &#xD;
            4. Obvious barrier to placing intra nasal catheters&#xD;
  &#xD;
            5. Have a known Do Not Attempt to Resuscitate (DNAR) order or other limitations in care&#xD;
  &#xD;
            6. Have a known terminal disease&#xD;
  &#xD;
            7. Known or clinically apparent pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>79 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Per Nordberg, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Karolinska Institutet</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Per Nordberg, MD, PhD</last_name>
      <phone>+46702802579</phone>
      <email>per.nordberg@ki.se</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Emelie Dillenbeck, MD</last_name>
      <phone>+46736484567</phone>
      <email>emelie.dillenbeck@regionstockholm.se</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University Hospital Vienna</name>
        <address>
          <city>Vienna</city>
          <country>Austria</country>
        </address>
      </facility>
      <contact>
        <last_name>Michael Holzer, MD, PhD</last_name>
        <email>michael.holzer@meduniwien.ac.at</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Erasme University Hospital</name>
        <address>
          <city>Brussels</city>
          <country>Belgium</country>
        </address>
      </facility>
      <contact>
        <last_name>Fabio S Taccone, MD, PhD</last_name>
        <email>fabio.taccone@ulb.be</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Charles University of Prague</name>
        <address>
          <city>Prague</city>
          <country>Czechia</country>
        </address>
      </facility>
      <contact>
        <last_name>Jan Belohlavek, Prof</last_name>
        <email>jan.belohlavek@vfn.cz</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University Hospital Freiburg</name>
        <address>
          <city>Freiburg</city>
          <country>Germany</country>
        </address>
      </facility>
      <contact>
        <last_name>Hans-Jörg Busch, MD, PhD</last_name>
        <email>hans-joerg.busch@uniklinik-freiburg.de</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ljubljana University Medical Centre</name>
        <address>
          <city>Ljubljana</city>
          <country>Slovenia</country>
        </address>
      </facility>
      <contact>
        <last_name>Peter Radsel, MD</last_name>
        <email>pradsel@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Austria</country>
      <country>Belgium</country>
      <country>Czechia</country>
      <country>Germany</country>
      <country>Slovenia</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>February 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
      <investigator_full_name>Per Nordberg</investigator_full_name>
      <investigator_title>Senior consultant in cardiology and intensive care, Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Therapeutic hypothermia</keyword>
    <keyword>transnasal cooling</keyword>
    <keyword>neurologic outcome</keyword>
    <keyword>ultrafast hypothermia</keyword>
    <keyword>prehospital</keyword>
    <keyword>ECPR</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Out-of-Hospital Cardiac Arrest</mesh_term>
      <mesh_term>Ventricular Fibrillation</mesh_term>
      <mesh_term>Hypothermia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06025123
  org study id: 2022-02446-01
  nct id: NCT06025123
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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)).
  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.
  primary purpose: Treatment
  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.
  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
  description: 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.
  measure: Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital
  time frame: Day 1
  measure: Proportion of patients alive at hospital discharge
  time frame: Day 1-90
  measure: Proportion of patients with Modified Rankin scale 0-3 at hospital discharge
  time frame: Day 1-90
  description: 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.
  measure: Proportion of patients alive at 90 days
  time frame: Day 90
  measure: Proportion of patients with Modified Rankin scale 0-3 at 90 days
  time frame: Day 90
  description: 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.
  measure: Device related adverse event rate within the first 24 hours
  time frame: Day 1
  description: Safety
  measure: Composite serious adverse event rate within the first 7 days
  time frame: Day 1-7
  description: Safety
  measure: Proportion of patients with new cardiac arrest prior to hospital admission
  time frame: Day 1
  description: Safety
  measure: Hospital-free days alive at 90 days
  time frame: Day 90
  measure: Distribution of modified Rankin scale at 90 days
  time frame: Day 90
  description: 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.
  measure: Distribution of Cerebral Performance Category scale at 90 days
  time frame: Day 90
  description: 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.
  measure: Proportion of patients alive after 1 year
  time frame: Day 365
  measure: Proportion of patients with Modified Rankin scale 0-1 at 1 year
  time frame: Day 365
  description: 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.
  measure: Quality of life assessed with EQ-5D-5L at 90 days
  time frame: Day 90
  description: 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.
  arm group label: Early transnasal evaporative cooling with the RhinoChill device
  arm group type: Experimental
  description: 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
  arm group label: Standard of care
  arm group type: No Intervention
  description: Standard advanced cardiac life support, subsequent fever control (Normothermia) for 72 hours at ICU
  intervention type: Device
  intervention name: Early transnasal evaporative cooling with the RhinoChill device
  description: Early prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours
  arm group label: Early transnasal evaporative cooling with the RhinoChill device
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 79 Years
  healthy volunteers: No
  last name: Per Nordberg, MD, PhD
  role: Principal Investigator
  affiliation: Karolinska Institutet
  last name: Per Nordberg, MD, PhD
  phone: +46702802579
  email: per.nordberg@ki.se
  last name: Emelie Dillenbeck, MD
  phone: +46736484567
  email: emelie.dillenbeck@regionstockholm.se
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: Austria
  country: Belgium
  country: Czechia
  country: Germany
  country: Slovenia
  responsible party type: Principal Investigator
  investigator affiliation: Karolinska Institutet
  investigator full name: Per Nordberg
  investigator title: Senior consultant in cardiology and intensive care, Associate Professor
  mesh term: Out-of-Hospital Cardiac Arrest
  mesh term: Ventricular Fibrillation
  mesh term: Hypothermia
  sharing ipd: No