Clinical trial NCT03826524: Epinephrine Dose: Optimal Versus Standard Evaluation Trial
Official title: CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Pfizer
First posted: 2019-02-01
Enrollment: 3790
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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 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

Primary outcomes:
measure: Survival to hospital discharge
timeFrame: Through study completion (up to 5 years)
Secondary outcomes:
measure: Return of spontaneous circulation in out-of-hospital setting
timeFrame: Through study completion (up to 5 years)
measure: Survival to emergency department arrival
timeFrame: Through study completion (up to 5 years)
measure: Survival to admission with death prior to discharge
timeFrame: Through study completion (up to 5 years)
measure: Survival to discharge outside of a long-term healthcare facility e.g. nursing home
timeFrame: Through study completion (up to 5 years)
measure: Modified Rankin Scale (mRS) score
timeFrame: 12+/-3 months
measure: Health Utility Index-3 (HUI-3) score
timeFrame: 12+/-3 months
measure: Hospital Anxiety and Depression Scale score
timeFrame: 12+/-3 months
measure: Length of stay in hospital
timeFrame: Through study completion (up to 5 years)
measure: Length of stay in critical care unit
timeFrame: Through study completion (up to 5 years)
measure: Survival post-arrest
timeFrame: Up to 5 years
measure: Recurrent cardiac arrest(s)
timeFrame: Up to 5 years
measure: ICD implant post-arrest
timeFrame: Up to 5 years
measure: Cardiovascular re-hospitalization(s)
timeFrame: Up to 5 years
measure: All-cause re-hospitalizations(s)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: British Columbia Emergency Health Services (BCEHS)
state: British Columbia
city: Halton
country: Canada
facility: Halton Region Paramedic Services
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Paramedic Services
state: Ontario
Study officials:
affiliation: St. Michael&#39;s Hospital
name: Paul Dorian, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Michael&#39;s Hospital
name: Steve Lin, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: