Early Amiodarone in Shockable Cardiac Arrest (Early-Amio)

Early Amiodarone in Shockable Cardiac Arrest (Early-Amio) Study

The primary objective of this pilot, pragmatic stepped-wedge cluster randomized trial is to evaluate if a modified cardiac arrest treatment algorithm calling for the administration of the initial amiodarone dose one 2-minute cycle earlier than current guidelines (during the same cycle as the initial dose of epinephrine) improves the time to amiodarone delivery in those with out-of-hospital cardiac arrest due to refractory ventricular fibrillation or ventricular tachycardia compared to usual care.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: Amiodarone Hydrochloride Injection; Other: Usual Care Protocol

Detailed Description

The primary objective of this pilot, pragmatic stepped-wedge cluster randomized trial is to evaluate if a modified cardiac arrest treatment algorithm calling for the administration of the initial amiodarone dose one 2-minute cycle earlier than current guidelines (during the same cycle as the initial dose of epinephrine) improves the time to amiodarone delivery in those with out-of-hospital cardiac arrest due to refractory ventricular fibrillation or ventricular tachycardia compared to usual care.

The null hypothesis is that there is no difference in time to amiodarone delivery, relative to emergency medical services (EMS) arrival on-scene or time of arrest if witnessed by EMS, in the modified protocol calling for earlier amiodarone administration compared to usual care.

Evaluated secondary outcomes will include the proportion of patients receiving amiodarone before their third defibrillation, pulses present at emergency department arrival, survival to hospital discharge, neurologically intact survival at hospital discharge, timing to other critical EMS interventions, and clinical adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 585
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Joshua Lupton, MD, MPH; Phone Number: (503) 418-6706; Email: lupton@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97035
      • Recruiting
      • Oregon Health & Sciences University
      • Contact: Joshua Lupton, MD, MPH; Phone Number: 503-418-6706; Email: lupton@ohsu.edu
      • Principal Investigator: Joshua Lupton, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Emergency medical services (EMS)-treated non-traumatic out-of-hospital cardiac arrest
• Initial rhythm on EMS rhythm assessment of ventricular fibrillation or ventricular tachycardia
• Recurrence or persistence of ventricular fibrillation or ventricular tachycardia after one defibrillation attempt

Exclusion Criteria:

• Known allergy to amiodarone
• EMS-assessed contraindication to amiodarone
• Pre-existing "do-not-attempt-resuscitation" orders
• Inter-facility transportations
• Initial care by a non-participating EMS agency able to perform advanced life support interventions
• Pediatric patient as determined by EMS
• Prisoners
• Pregnant patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Amiodarone Protocol; Amiodarone administration after the second defibrillator shock, during the same two-minute cycle as the initial dose of epinephrine.	Drug: Amiodarone Hydrochloride Injection; The use of a modified treatment protocol by emergency medical services where the initial dose of amiodarone is given after the second defibrillator shock, during the same two-minute cycle as the initial dose of epinephrine, for out-of-hospital cardiac arrest due to a shockable rhythm (ventricular fibrillation or ventricular tachycardia) that is persistent or recurs after at least one defibrillation attempt. If an EMS agency is assigned to this arm, no downstream care after the initial dose of amiodarone is dictated by the study.; Other Names: Early-Amiodarone Protocol
Active Comparator: Usual Care Protocol; Amiodarone administration after the third defibrillator shock, one two-minute cycle after the initial dose of epinephrine.	Other: Usual Care Protocol; The use of a usual care treatment protocol by emergency medical services where the initial dose of amiodarone is given after the third defibrillator shock, one two-minute cycle after the initial dose of epinephrine, for out-of-hospital cardiac arrest due to a shockable rhythm (ventricular fibrillation or ventricular tachycardia) that is persistent or recurs after at least one defibrillation attempt. If an EMS agency is assigned to this arm, no downstream care after the initial dose of amiodarone is dictated by the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time from emergency medical services (EMS) arrival on-scene (or time of arrest if witnessed by EMS) to the administration of the initial dose of amiodarone in minutes	up to 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and proportion of patients receiving the initial dose of amiodarone from emergency medical services before the third shock from a defibrillator		up to 1 day
The number and proportion of patients with pulses present and documented by emergency medical services at the time of patient care transfer to hospital staff at emergency department arrival		up to 1 day
The number and proportion of patients surviving to be admitted to inpatient services after arrival to the emergency department		up to 1 day
The number and proportion of patients surviving to be discharged from the hospital (or 30 days, whichever is sooner) after their admission for cardiac arrest		up to 30 days
The number and proportion of patients surviving to be discharged from the hospital (or 30 days, whichever is sooner) after their admission for cardiac arrest with a Cerebral Performance Category score of 1 or 2	The Cerebral Performance Category (CPC) score scale is 1-5: CPC 1: Good cerebral performance: conscious, alert, able to work, might have mild neurologic or psychologic deficit. CPC 2: Moderate cerebral disability: conscious, sufficient cerebral function for independent activities of daily life. Able to work in sheltered environment. CPC 3: Severe cerebral disability: conscious, dependent on others for daily support because of impaired brain function. Ranges from ambulatory state to severe dementia or paralysis. CPC 4: Coma or vegetative state: any degree of coma without the presence of all brain death criteria. Unawareness, even if appears awake (vegetative state) without interaction with environment; may have spontaneous eye opening and sleep/awake cycles. Cerebral unresponsiveness. CPC 5: Brain death: apnea, areflexia, EEG silence, etc.	up to 30 days
Time from emergency medical services (EMS) arrival on-scene (or time of arrest if witnessed by EMS) to the delivery of other critical interventions in minutes	Critical interventions include: the second-fourth defibrillator shocks, the first use of double sequential external defibrillation, the administration of the first two epinephrine doses, and the time to advanced airway placement by EMS.	up to 1 day
Number and proportion of participants with adverse events	e.g.: malignant cardiac arrhythmia, allergic reaction, recurrent cardiac arrest	up to 1 day

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Joshua Lupton, MD, MPH, Oregon Health and Science University

Publications and helpful links

Helpful Links

• Early-Amio Study Website

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzofurans; Amiodarone
• Other Study ID Numbers: STUDY00026455; 1K23HL173647-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A de-identified dataset will be shared with all data elements required for analysis, if de-identification is deemed feasible, with the NHLBI BioLINCC.
• IPD Sharing Time Frame: Within 12 months from study completion. No end date.
• IPD Sharing Access Criteria: Per NHLBI BioLINCC policy
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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