<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/NCT03826524</url>
  </required_header>
  <id_info>
    <org_study_id>EpiDOSE Protocol Version 2.2</org_study_id>
    <nct_id>NCT03826524</nct_id>
  </id_info>
  <brief_title>Epinephrine Dose: Optimal Versus Standard Evaluation Trial</brief_title>
  <acronym>EpiDOSE</acronym>
  <official_title>CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Unity Health Toronto</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 objective of this randomized controlled trial is to evaluate the effectiveness of a low&#xD;
      cumulative dose of epinephrine compared to a standard cumulative dose of epinephrine during&#xD;
      resuscitation from ventricular fibrillation (VF) or ventricular tachycardia (VT) in adult&#xD;
      out-of-hospital cardiac arrest (OHCA) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a prospective, multicentre, single-blinded randomized controlled&#xD;
      trial (RCT) where eligible OHCA patients are randomized to receive a low cumulative dose of&#xD;
      epinephrine (low dose epinephrine, up to 2mg total) or a standard cumulative dose of&#xD;
      epinephrine (standard dose epinephrine, up to 6mg total) in a 1:1 fashion.&#xD;
&#xD;
      Eligible OHCA patients will be treated by emergency medical service (EMS) providers who will&#xD;
      initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per&#xD;
      EMS treatment protocols. After one defibrillation and when feasible, EMS providers will&#xD;
      establish peripheral intravenous (IV) access, and patients will be randomly allocated to 1 of&#xD;
      the 2 study arms. Subsequent study drug doses will be administered every 3-5 minutes, based&#xD;
      on current guidelines and paramedic protocols, during resuscitation until the first return of&#xD;
      spontaneous circulation (ROSC) is achieved or if resuscitation has been terminated by the&#xD;
      base hospital physician. Other medications (e.g. antiarrhythmics, magnesium, beta blockers)&#xD;
      and interventions (e.g. intubation) may be interposed as required. Follow-up will take place&#xD;
      using a combination of administrative databases (e.g. the Discharge Abstract Database and the&#xD;
      National Ambulatory Care Reporting System) and telephone interviews.&#xD;
&#xD;
      This RCT will evaluate a fundamental change in the treatment of OHCA. The investigators&#xD;
      hypothesize that a low cumulative dose of epinephrine will improve patient survival to&#xD;
      hospital discharge compared to a standard cumulative dose of epinephrine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 24, 2023</start_date>
  <completion_date type="Anticipated">June 2028</completion_date>
  <primary_completion_date type="Anticipated">December 2027</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival to hospital discharge</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Individuals discharged alive from hospital</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Return of spontaneous circulation in out-of-hospital setting</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Return of spontaneous circulation in the field</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival to emergency department arrival</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Individuals alive upon arrival to a hospital emergency department</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival to admission with death prior to discharge</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Individuals alive upon hospital admission who die in-hospital before being discharged</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival to discharge outside of a long-term healthcare facility e.g. nursing home</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Individuals discharged alive from hospital to a care facility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale (mRS) score</measure>
    <time_frame>12+/-3 months</time_frame>
    <description>Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Utility Index-3 (HUI-3) score</measure>
    <time_frame>12+/-3 months</time_frame>
    <description>Assessment of quality of life, scores range from -0.36 to 1 where higher scores indicate better quality life (negative scores=a state worse than being dead, 0=dead, 1=perfect health)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression Scale score</measure>
    <time_frame>12+/-3 months</time_frame>
    <description>Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in hospital</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Length of time an individual remained in-hospital (length in days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in critical care unit</measure>
    <time_frame>Through study completion (up to 5 years)</time_frame>
    <description>Length of time an individual remained in a crucial care unit (length in days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival post-arrest</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Survival following hospital discharge, up to 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent cardiac arrest(s)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Number of cardiac arrests following the index arrest</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICD implant post-arrest</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Whether an implantable cardioverter defibrillator was implanted post-arrest</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular re-hospitalization(s)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Number of cardiovascular re-hospitalizations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause re-hospitalizations(s)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Number of re-hospitalizations for any reason</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">3790</enrollment>
  <condition>Cardiac Arrest, Out-Of-Hospital</condition>
  <condition>Sudden Cardiac Arrest</condition>
  <condition>Ventricular Fibrillation</condition>
  <condition>Ventricular Tachycardia-Pulseless</condition>
  <arm_group>
    <arm_group_label>Low Dose Epinephrine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Epinephrine up to 2mg total</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Dose Epinephrine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Epinephrine up to 6mg total</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epinephrine</intervention_name>
    <description>Epinephrine 1mg 1:10000 (10cc) per dose</description>
    <arm_group_label>Low Dose Epinephrine</arm_group_label>
    <arm_group_label>Standard Dose Epinephrine</arm_group_label>
    <other_name>Adrenaline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Out-of-hospital cardiac arrest treated by paramedics&#xD;
&#xD;
          -  Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis&#xD;
             administered or witnessed by EMS (paramedic or fire)&#xD;
&#xD;
          -  Established intravenous vascular access&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or apparent age &lt;18 years&#xD;
&#xD;
          -  Initial recorded cardiac rhythm of pulseless electrical activity or asystole&#xD;
&#xD;
          -  Cardiac arrest due to an obvious non-cardiac primary cause (e.g. blunt or penetrating&#xD;
             trauma, exsanguination, burns, drug overdose, drowning, anaphylaxis, sudden&#xD;
             asphyxiation, etc.)&#xD;
&#xD;
          -  Prisoners or persons in police custody&#xD;
&#xD;
          -  Known allergy or sensitivity to epinephrine&#xD;
&#xD;
          -  Prior receipt of non-study kit intravenous, intraosseous, or intramuscular epinephrine&#xD;
             during resuscitation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Dorian, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Unity Health Toronto</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steve Lin, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Unity Health Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Theresa Aves, MSc</last_name>
    <phone>416-864-6060</phone>
    <phone_ext>46787</phone_ext>
    <email>theresa.aves@unityhealth.to</email>
  </overall_contact>
  <location>
    <facility>
      <name>Halton Region Paramedic Services</name>
      <address>
        <city>Halton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Theresa Aves</last_name>
      <phone>416-864-6060</phone>
      <phone_ext>46787</phone_ext>
    </contact>
    <investigator>
      <last_name>Sheldon Cheskes, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 7, 2018</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>out-of-hospital cardiac arrest</keyword>
  <keyword>sudden cardiac arrest</keyword>
  <keyword>epinephrine</keyword>
  <keyword>randomized controlled trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Arrest</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Tachycardia, Ventricular</mesh_term>
    <mesh_term>Ventricular Fibrillation</mesh_term>
    <mesh_term>Death, Sudden, Cardiac</mesh_term>
    <mesh_term>Out-of-Hospital Cardiac Arrest</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epinephrine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03826524
org study id: EpiDOSE Protocol Version 2.2
nct id: NCT03826524
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this randomized controlled trial is to evaluate the effectiveness of a low
      cumulative dose of epinephrine compared to a standard cumulative dose of epinephrine during
      resuscitation from ventricular fibrillation (VF) or ventricular tachycardia (VT) in adult
      out-of-hospital cardiac arrest (OHCA) patients.
This study is designed as a prospective, multicentre, single-blinded randomized controlled
      trial (RCT) where eligible OHCA patients are randomized to receive a low cumulative dose of
      epinephrine (low dose epinephrine, up to 2mg total) or a standard cumulative dose of
      epinephrine (standard dose epinephrine, up to 6mg total) in a 1:1 fashion.

      Eligible OHCA patients will be treated by emergency medical service (EMS) providers who will
      initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per
      EMS treatment protocols. After one defibrillation and when feasible, EMS providers will
      establish peripheral intravenous (IV) access, and patients will be randomly allocated to 1 of
      the 2 study arms. Subsequent study drug doses will be administered every 3-5 minutes, based
      on current guidelines and paramedic protocols, during resuscitation until the first return of
      spontaneous circulation (ROSC) is achieved or if resuscitation has been terminated by the
      base hospital physician. Other medications (e.g. antiarrhythmics, magnesium, beta blockers)
      and interventions (e.g. intubation) may be interposed as required. Follow-up will take place
      using a combination of administrative databases (e.g. the Discharge Abstract Database and the
      National Ambulatory Care Reporting System) and telephone interviews.

      This RCT will evaluate a fundamental change in the treatment of OHCA. The investigators
      hypothesize that a low cumulative dose of epinephrine will improve patient survival to
      hospital discharge compared to a standard cumulative dose of epinephrine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Survival to hospital discharge
time frame: Through study completion (up to 5 years)
description: Individuals discharged alive from hospital
measure: Return of spontaneous circulation in out-of-hospital setting
time frame: Through study completion (up to 5 years)
description: Return of spontaneous circulation in the field
measure: Survival to emergency department arrival
time frame: Through study completion (up to 5 years)
description: Individuals alive upon arrival to a hospital emergency department
measure: Survival to admission with death prior to discharge
time frame: Through study completion (up to 5 years)
description: Individuals alive upon hospital admission who die in-hospital before being discharged
measure: Survival to discharge outside of a long-term healthcare facility e.g. nursing home
time frame: Through study completion (up to 5 years)
description: Individuals discharged alive from hospital to a care facility
measure: Modified Rankin Scale (mRS) score
time frame: 12+/-3 months
description: Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead)
measure: Health Utility Index-3 (HUI-3) score
time frame: 12+/-3 months
description: Assessment of quality of life, scores range from -0.36 to 1 where higher scores indicate better quality life (negative scores=a state worse than being dead, 0=dead, 1=perfect health)
measure: Hospital Anxiety and Depression Scale score
time frame: 12+/-3 months
description: Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression
measure: Length of stay in hospital
time frame: Through study completion (up to 5 years)
description: Length of time an individual remained in-hospital (length in days)
measure: Length of stay in critical care unit
time frame: Through study completion (up to 5 years)
description: Length of time an individual remained in a crucial care unit (length in days)
measure: Survival post-arrest
time frame: Up to 5 years
description: Survival following hospital discharge, up to 5 years
measure: Recurrent cardiac arrest(s)
time frame: Up to 5 years
description: Number of cardiac arrests following the index arrest
measure: ICD implant post-arrest
time frame: Up to 5 years
description: Whether an implantable cardioverter defibrillator was implanted post-arrest
measure: Cardiovascular re-hospitalization(s)
time frame: Up to 5 years
description: Number of cardiovascular re-hospitalizations
measure: All-cause re-hospitalizations(s)
time frame: Up to 5 years
description: Number of re-hospitalizations for any reason
arm group label: Low Dose Epinephrine
arm group type: Active Comparator
description: Epinephrine up to 2mg total
arm group label: Standard Dose Epinephrine
arm group type: Active Comparator
description: Epinephrine up to 6mg total
intervention type: Drug
intervention name: Epinephrine
description: Epinephrine 1mg 1:10000 (10cc) per dose
arm group label: Low Dose Epinephrine
arm group label: Standard Dose Epinephrine
other name: Adrenaline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Dorian, MD, MSc
role: Principal Investigator
affiliation: Unity Health Toronto
last name: Steve Lin, MD, MSc
role: Principal Investigator
affiliation: Unity Health Toronto
last name: Theresa Aves, MSc
phone: 416-864-6060
phone ext: 46787
email: theresa.aves@unityhealth.to
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: Heart Arrest
mesh term: Tachycardia
mesh term: Tachycardia, Ventricular
mesh term: Ventricular Fibrillation
mesh term: Death, Sudden, Cardiac
mesh term: Out-of-Hospital Cardiac Arrest
mesh term: Epinephrine
sharing ipd: No