Cardiac Arrest, Out-Of-HospitalPhase 4EpiDOSENCT03826524
Epinephrine Dose: Optimal Versus Standard Evaluation Trial
A Phase 4 study testing Epinephrine in people with Cardiac Arrest, Out-Of-Hospital and Sudden Cardiac Arrest, run by Unity Health Toronto at 9 sites in Canada.
Trial summary
The objective of this randomized controlled trial is to evaluate whether a low cumulative dose of epinephrine ("low dose") is non-inferior to a standard cumulative dose of epinephrine ("standard dose") with respect to survival to hospital discharge among adults undergoing resuscitation for OHCA due to ventricular… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Arrest, Out-Of-Hospital, Sudden Cardiac Arrest, Ventricular Fibrillation
- What is being tested?
- Epinephrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,250 participants
- Where
- 9 sitesCanada
- Study dates
- 24 May 2023to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Out-of-hospital cardiac arrest treated by paramedics AND
- Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or confirmed by paramedics or fire services, AND
- Established intravenous vascular access
Who cannot join
- Known or apparent age <18 years
- Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or confirmed by paramedics
- 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.)
- Administration of intramuscular, endotracheal tube, or intraosseous epinephrine
- Prisoners or persons in police custody
- Known allergy or sensitivity to epinephrine
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Canada9 sites, 9 recruiting
- Recruiting
Peel Regional Paramedic Services
Brampton, Ontario, L6T 4B9
Theresa Aves, 416-864-6060 ext. 46787, theresa.aves@unityhealth.to
Sheldon Cheskes, MD
- Recruiting
Middlesex-London Paramedic Service
London, Ontario, N6E 1R4
Manya Charette, 613-798-5555 ext. 17758, mancharette@ohri.ca
Christian Vaillancourt, MD
- Recruiting
Halton Region Paramedic Services
Oakville, Ontario, L6M 3L1
Theresa Aves, 416-864-6060 ext. 46787, epidose@unityhealth.to
Sheldon Cheskes, MD
- Recruiting
Ottawa Paramedic Services
Ottawa, Ontario, K1H 1E2
Manya Charette, 613-798-5555 ext. 17758, mancharette@ohri.ca
Christian Vaillancourt, MD
- Recruiting
Medavie Health Services West
Saskatoon, Saskatchewan, S7J 4M2
Tracy Wilson, PhD, 306-655-2810, tracy.wilson@usask.ca
Andrew Leach, MD
- Recruiting
Superior North Emergency Medical Services
Thunder Bay, Ontario, P7B 4X6
Manya Charette, 613-798-5555 ext. 17758, mancharette@ohri.ca
Christian Vaillancourt, MD
- Recruiting
British Columbia Emergency Health Services (BCEHS)
Victoria, British Columbia, V8W 9P1
Helen Connolly, 604-806-8753, HConnolly@providencehealth.bc.ca
Brian Grunau, MD
- Recruiting
Region of Waterloo Paramedic Services
Waterloo, Ontario, N2G 4J3
Kathy Winter, MD, 905-521-2100 ext. 71223, winterkat@hhsc.ca
Paul Miller, MD
- Recruiting
Essex-Windsor Emergency Health Services
Windsor, Ontario, N9A 1N6
Manya Charette, 613-798-5555 ext. 17758, mancharette@ohri.ca
Christian Vaillancourt, MD
About this study
Official title: CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)
The objective of this randomized controlled trial is to evaluate whether a low cumulative dose of epinephrine ("low dose") is non-inferior to a standard cumulative dose of epinephrine ("standard dose") with respect to survival to hospital discharge among adults undergoing resuscitation for OHCA due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT).
Read the 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 paramedics who will initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per paramedic agencies' treatment protocols. After one defibrillation and when feasible, paramedics will establish peripheral intravenous (IV) access, and patients will be randomly allocated to either the low dose or standard dose treatment arm. Epinephrine doses (according to treatment assignment) will be administered every 3-5 minutes, based on current guidelines and paramedic protocols, 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. Please feel free to contact epidose@unityhealth.to for further information.
- Conditions
- Cardiac Arrest, Out-Of-Hospital, Sudden Cardiac Arrest, Ventricular Fibrillation, Ventricular Tachycardia-Pulseless
- Being tested
- Epinephrine
- Keywords
- out-of-hospital cardiac arrest, sudden cardiac arrest, epinephrine, randomized controlled trial
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Death, Sudden, Cardiac, Ventricular Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpinephrineDrug
Also called Adrenaline
Epinephrine 1mg 1:10000 (10cc) per dose
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Epinephrine | Active comparator | Epinephrine up to 2mg total Receives: Drug: Epinephrine |
| Standard Dose Epinephrine | Active comparator | Epinephrine up to 6mg total Receives: Drug: Epinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival to hospital discharge
Individuals discharged alive from hospital
Measured: Through study completion (up to 5 years)
Secondary outcomes (14)
Return of spontaneous circulation in out-of-hospital setting
Return of spontaneous circulation in the field
Measured: Through study completion (up to 5 years)
Survival to emergency department arrival
Individuals alive upon arrival to a hospital emergency department
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: 12+/-3 months
Length of stay in hospital
Length of time an individual remained in-hospital (length in days)
Measured: 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)
Measured: Through study completion (up to 5 years)
Survival post-arrest
Survival following hospital discharge, up to 5 years
Measured: Up to 5 years
Recurrent cardiac arrest(s)
Number of cardiac arrests following the index arrest
Measured: Up to 5 years
ICD implant post-arrest
Whether an implantable cardioverter defibrillator was implanted post-arrest
Measured: Up to 5 years
Cardiovascular re-hospitalization(s)
Number of cardiovascular re-hospitalizations
Measured: Up to 5 years
All-cause re-hospitalizations(s)
Number of re-hospitalizations for any reason
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start24 May 2023
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac Arrest, Out-Of-HospitalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Paul Dorian, MD, MSc, Principal investigator, Unity Health TorontoSteve Lin, MD, MSc, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03826524
- Sponsor's protocol ID
- EpiDOSE Protocol Version 4.0
- Acronym
- EpiDOSE
- Status last verified
- Dec 2025
- First submitted
- 7 Nov 2018
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)
- ClinicalTrials.gov ID
- NCT03826524
- Acronym / sponsor ID
- EpiDOSE / EpiDOSE Protocol Version 4.0
- Conditions
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,250 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 24 May 2023 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this randomized controlled trial is to evaluate whether a low cumulative dose of epinephrine ("low dose") is non-inferior to a standard cumulative dose of epinephrine ("standard dose") with respect to survival to hospital discharge among adults undergoing resuscitation for OHCA due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT).
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 paramedics who will initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per paramedic agencies' treatment protocols. After one defibrillation and when feasible, paramedics will establish peripheral intravenous (IV) access, and patients will be randomly allocated to either the low dose or standard dose treatment arm. Epinephrine doses (according to treatment assignment) will be administered every 3-5 minutes, based on current guidelines and paramedic protocols, 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. Please feel free to contact epidose@unityhealth.to for further information.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Dose Epinephrine | Active comparator | Drug: EpinephrineEpinephrine up to 2mg total |
| Standard Dose Epinephrine | Active comparator | Drug: EpinephrineEpinephrine up to 6mg total |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Out-of-hospital cardiac arrest treated by paramedics AND
- Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or confirmed by paramedics or fire services, AND
- Established intravenous vascular access
Key exclusion criteria (6 listed)
- Known or apparent age <18 years
- Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or confirmed by paramedics
- 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.)
- Administration of intramuscular, endotracheal tube, or intraosseous epinephrine
- Prisoners or persons in police custody
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpinephrineAlso: AdrenalineEpinephrine 1mg 1:10000 (10cc) per dose | Drug | Low Dose Epinephrine, Standard Dose Epinephrine |
Primary outcome
Survival to hospital discharge
Time frame: Through study completion (up to 5 years)
Individuals discharged alive from hospital
14 secondary outcomes
Return of spontaneous circulation in out-of-hospital setting
Time frame: Through study completion (up to 5 years)
Survival to emergency department arrival
Time frame: Through study completion (up to 5 years)
Survival to admission with death prior to discharge
Time frame: Through study completion (up to 5 years)
Survival to discharge outside of a long-term healthcare facility e.g. nursing home
Time frame: Through study completion (up to 5 years)
Modified Rankin Scale (mRS) score
Time frame: 12+/-3 months
Health Utility Index-3 (HUI-3) score
Time frame: 12+/-3 months
Hospital Anxiety and Depression Scale score
Time frame: 12+/-3 months
Length of stay in hospital
Time frame: Through study completion (up to 5 years)
Length of stay in critical care unit
Time frame: Through study completion (up to 5 years)
Survival post-arrest
Time frame: Up to 5 years
Recurrent cardiac arrest(s)
Time frame: Up to 5 years
ICD implant post-arrest
Time frame: Up to 5 years
Cardiovascular re-hospitalization(s)
Time frame: Up to 5 years
All-cause re-hospitalizations(s)
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Dorian, MD, MSc principal investigator
Unity Health Toronto
Steve Lin, MD, MSc principal investigator
Unity Health Toronto
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Epinephrine in people with Cardiac Arrest, Out-Of-Hospital and Sudden Cardiac Arrest, run by Unity Health Toronto at 9 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Theresa Aves, MSc (416-864-6060 ext. 46787, theresa.aves@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival to hospital discharge (time frame: Through study completion (up to 5 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026; AzTrials last refreshed its copy on 28 Oct 2026.