Epinephrine Dose: Optimal Versus Standard Evaluation Trial (EpiDOSE)

CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)

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.

Study Overview

• Status: Recruiting
• Conditions: Ventricular Fibrillation; Sudden Cardiac Arrest; Cardiac Arrest, Out-Of-Hospital; Ventricular Tachycardia-Pulseless
• Intervention / Treatment: Drug: Epinephrine

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.

• Study Type: Interventional
• Enrollment (Estimated): 3790
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Theresa Aves, MSc; Phone Number: 46787 416-864-6060; Email: theresa.aves@unityhealth.to

Study Locations

• Canada
  • Ontario
    • Halton, Ontario, Canada
      • Recruiting
      • Halton Region Paramedic Services
      • Contact: Theresa Aves; Phone Number: 46787 416-864-6060
      • Principal Investigator: Sheldon Cheskes, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Dose Epinephrine; Epinephrine up to 2mg total	Drug: Epinephrine; Epinephrine 1mg 1:10000 (10cc) per dose; Other Names: Adrenaline
Active Comparator: Standard Dose Epinephrine; Epinephrine up to 6mg total	Drug: Epinephrine; Epinephrine 1mg 1:10000 (10cc) per dose; Other Names: Adrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to hospital discharge	Individuals discharged alive from hospital	Through study completion (up to 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return of spontaneous circulation in out-of-hospital setting	Return of spontaneous circulation in the field	Through study completion (up to 5 years)
Survival to emergency department arrival	Individuals alive upon arrival to a hospital emergency department	Through study completion (up to 5 years)
Survival to admission with death prior to discharge	Individuals alive upon hospital admission who die in-hospital before being discharged	Through study completion (up to 5 years)
Survival to discharge outside of a long-term healthcare facility e.g. nursing home	Individuals discharged alive from hospital to a care facility	Through study completion (up to 5 years)
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)	12+/-3 months
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)	12+/-3 months
Hospital Anxiety and Depression Scale score	Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression	12+/-3 months
Length of stay in hospital	Length of time an individual remained in-hospital (length in days)	Through study completion (up to 5 years)
Length of stay in critical care unit	Length of time an individual remained in a crucial care unit (length in days)	Through study completion (up to 5 years)
Survival post-arrest	Survival following hospital discharge, up to 5 years	Up to 5 years
Recurrent cardiac arrest(s)	Number of cardiac arrests following the index arrest	Up to 5 years
ICD implant post-arrest	Whether an implantable cardioverter defibrillator was implanted post-arrest	Up to 5 years
Cardiovascular re-hospitalization(s)	Number of cardiovascular re-hospitalizations	Up to 5 years
All-cause re-hospitalizations(s)	Number of re-hospitalizations for any reason	Up to 5 years

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Pfizer; Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Paul Dorian, MD, MSc, Unity Health Toronto; Principal Investigator: Steve Lin, MD, MSc, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: randomized controlled trial; out-of-hospital cardiac arrest; epinephrine; sudden cardiac arrest
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Death; Heart Arrest; Ventricular Fibrillation; Tachycardia; Tachycardia, Ventricular; Out-of-Hospital Cardiac Arrest; Death, Sudden, Cardiac; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine
• Other Study ID Numbers: EpiDOSE Protocol Version 2.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No