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Epinephrine Dose: Optimal Versus Standard Evaluation Trial

Phase 4
Recruiting
Conditions
Sudden Cardiac Arrest
Cardiac Arrest, Out-Of-Hospital
Ventricular Fibrillation
Ventricular Tachycardia-Pulseless
Interventions
Registration Number
NCT03826524
Lead Sponsor
Unity Health Toronto
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
3790
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low Dose EpinephrineEpinephrineEpinephrine up to 2mg total
Standard Dose EpinephrineEpinephrineEpinephrine up to 6mg total
Primary Outcome Measures
NameTimeMethod
Survival to hospital dischargeThrough study completion (up to 5 years)

Individuals discharged alive from hospital

Secondary Outcome Measures
NameTimeMethod
Survival post-arrestUp to 5 years

Survival following hospital discharge, up to 5 years

ICD implant post-arrestUp to 5 years

Whether an implantable cardioverter defibrillator was implanted post-arrest

Survival to admission with death prior to dischargeThrough study completion (up to 5 years)

Individuals alive upon hospital admission who die in-hospital before being discharged

Recurrent cardiac arrest(s)Up to 5 years

Number of cardiac arrests following the index arrest

All-cause re-hospitalizations(s)Up to 5 years

Number of re-hospitalizations for any reason

Return of spontaneous circulation in out-of-hospital settingThrough study completion (up to 5 years)

Return of spontaneous circulation in the field

Survival to emergency department arrivalThrough study completion (up to 5 years)

Individuals alive upon arrival to a hospital emergency department

Survival to discharge outside of a long-term healthcare facility e.g. nursing homeThrough study completion (up to 5 years)

Individuals discharged alive from hospital to a care facility

Modified Rankin Scale (mRS) score12+/-3 months

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) score12+/-3 months

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 score12+/-3 months

Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression

Length of stay in hospitalThrough study completion (up to 5 years)

Length of time an individual remained in-hospital (length in days)

Length of stay in critical care unitThrough study completion (up to 5 years)

Length of time an individual remained in a crucial care unit (length in days)

Cardiovascular re-hospitalization(s)Up to 5 years

Number of cardiovascular re-hospitalizations

Trial Locations

Locations (3)

British Columbia Emergency Health Services (BCEHS)

🇨🇦

Victoria, British Columbia, Canada

Ottawa Paramedic Services

🇨🇦

Ottawa, Ontario, Canada

Halton Region Paramedic Services

🇨🇦

Halton, Ontario, Canada

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