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Epinephrine Dose: Optimal Versus Standard Evaluation Trial (EpiDOSE)

Primary Purpose

Cardiac Arrest, Out-Of-Hospital, Sudden Cardiac Arrest, Ventricular Fibrillation

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Epinephrine
Sponsored by
Unity Health Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest, Out-Of-Hospital focused on measuring out-of-hospital cardiac arrest, sudden cardiac arrest, epinephrine, randomized controlled trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Out-of-hospital cardiac arrest treated by paramedics
  2. Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or witnessed by EMS (paramedic or fire)
  3. Established intravenous vascular access

Exclusion Criteria:

  1. Known or apparent age <18 years
  2. Initial recorded cardiac rhythm of pulseless electrical activity or asystole
  3. Cardiac arrest due to an obvious non-cardiac primary cause (e.g. blunt or penetrating trauma, exsanguination, burns, drug overdose, drowning, anaphylaxis, sudden asphyxiation, etc.)
  4. Prior receipt of non-study kit intravenous or intramuscular epinephrine during resuscitation

Sites / Locations

  • Halton Region Paramedic ServicesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Low Dose Epinephrine

Standard Dose Epinephrine

Arm Description

Epinephrine up to 2mg total

Epinephrine up to 6mg total

Outcomes

Primary Outcome Measures

Survival to hospital discharge
Individuals discharged alive from hospital

Secondary Outcome Measures

Return of spontaneous circulation in out-of-hospital setting
Return of spontaneous circulation in the field
Survival to emergency department arrival
Individuals alive upon arrival to a hospital emergency department
Survival to admission with death prior to discharge
Individuals alive upon hospital admission who die in-hospital before being discharged
Survival to discharge outside of a long-term healthcare facility e.g. nursing home
Individuals discharged alive from hospital to a care facility
Modified Rankin Scale (mRS) score
Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead)
Health Utility Index-3 (HUI-3) score
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)
Hospital Anxiety and Depression Scale score
Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression
Length of stay in hospital
Length of time an individual remained in-hospital (length in days)
Length of stay in critical care unit
Length of time an individual remained in a crucial care unit (length in days)
Survival post-arrest
Survival following hospital discharge, up to 5 years
Recurrent cardiac arrest(s)
Number of cardiac arrests following the index arrest
ICD implant post-arrest
Whether an implantable cardioverter defibrillator was implanted post-arrest
Cardiovascular re-hospitalization(s)
Number of cardiovascular re-hospitalizations
All-cause re-hospitalizations(s)
Number of re-hospitalizations for any reason

Full Information

First Posted
November 7, 2018
Last Updated
June 6, 2023
Sponsor
Unity Health Toronto
Collaborators
Canadian Institutes of Health Research (CIHR), Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03826524
Brief Title
Epinephrine Dose: Optimal Versus Standard Evaluation Trial
Acronym
EpiDOSE
Official Title
CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 24, 2023 (Actual)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
June 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Unity Health Toronto
Collaborators
Canadian Institutes of Health Research (CIHR), Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest, Out-Of-Hospital, Sudden Cardiac Arrest, Ventricular Fibrillation, Ventricular Tachycardia-Pulseless
Keywords
out-of-hospital cardiac arrest, sudden cardiac arrest, epinephrine, randomized controlled trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3790 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Dose Epinephrine
Arm Type
Active Comparator
Arm Description
Epinephrine up to 2mg total
Arm Title
Standard Dose Epinephrine
Arm Type
Active Comparator
Arm Description
Epinephrine up to 6mg total
Intervention Type
Drug
Intervention Name(s)
Epinephrine
Other Intervention Name(s)
Adrenaline
Intervention Description
Epinephrine 1mg 1:10000 (10cc) per dose
Primary Outcome Measure Information:
Title
Survival to hospital discharge
Description
Individuals discharged alive from hospital
Time Frame
Through study completion (up to 5 years)
Secondary Outcome Measure Information:
Title
Return of spontaneous circulation in out-of-hospital setting
Description
Return of spontaneous circulation in the field
Time Frame
Through study completion (up to 5 years)
Title
Survival to emergency department arrival
Description
Individuals alive upon arrival to a hospital emergency department
Time Frame
Through study completion (up to 5 years)
Title
Survival to admission with death prior to discharge
Description
Individuals alive upon hospital admission who die in-hospital before being discharged
Time Frame
Through study completion (up to 5 years)
Title
Survival to discharge outside of a long-term healthcare facility e.g. nursing home
Description
Individuals discharged alive from hospital to a care facility
Time Frame
Through study completion (up to 5 years)
Title
Modified Rankin Scale (mRS) score
Description
Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead)
Time Frame
12+/-3 months
Title
Health Utility Index-3 (HUI-3) score
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)
Time Frame
12+/-3 months
Title
Hospital Anxiety and Depression Scale score
Description
Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression
Time Frame
12+/-3 months
Title
Length of stay in hospital
Description
Length of time an individual remained in-hospital (length in days)
Time Frame
Through study completion (up to 5 years)
Title
Length of stay in critical care unit
Description
Length of time an individual remained in a crucial care unit (length in days)
Time Frame
Through study completion (up to 5 years)
Title
Survival post-arrest
Description
Survival following hospital discharge, up to 5 years
Time Frame
Up to 5 years
Title
Recurrent cardiac arrest(s)
Description
Number of cardiac arrests following the index arrest
Time Frame
Up to 5 years
Title
ICD implant post-arrest
Description
Whether an implantable cardioverter defibrillator was implanted post-arrest
Time Frame
Up to 5 years
Title
Cardiovascular re-hospitalization(s)
Description
Number of cardiovascular re-hospitalizations
Time Frame
Up to 5 years
Title
All-cause re-hospitalizations(s)
Description
Number of re-hospitalizations for any reason
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Out-of-hospital cardiac arrest treated by paramedics Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or witnessed by EMS (paramedic or fire) Established intravenous vascular access Exclusion Criteria: Known or apparent age <18 years Initial recorded cardiac rhythm of pulseless electrical activity or asystole Cardiac arrest due to an obvious non-cardiac primary cause (e.g. blunt or penetrating trauma, exsanguination, burns, drug overdose, drowning, anaphylaxis, sudden asphyxiation, etc.) Prisoners or persons in police custody Known allergy or sensitivity to epinephrine Prior receipt of non-study kit intravenous, intraosseous, or intramuscular epinephrine during resuscitation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Theresa Aves, MSc
Phone
416-864-6060
Ext
46787
Email
theresa.aves@unityhealth.to
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Dorian, MD, MSc
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steve Lin, MD, MSc
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Halton Region Paramedic Services
City
Halton
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Theresa Aves
Phone
416-864-6060
Ext
46787
First Name & Middle Initial & Last Name & Degree
Sheldon Cheskes, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Epinephrine Dose: Optimal Versus Standard Evaluation Trial

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