Amiodarone for Cardiac Arrest

(Early-Amio Trial)

Overseen By Joshua Lupton, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Oregon Health and Science University

Disqualifiers: Allergy to amiodarone, Do-not-resuscitate, Pediatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate (during cardiac arrest event)

585 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether administering an earlier dose of amiodarone, an antiarrhythmic medication, can enhance treatment during cardiac arrest. It focuses on individuals with specific heart rhythm issues, such as ventricular fibrillation or ventricular tachycardia, that persist after one defibrillator shock. Participants will either receive the drug earlier than usual or adhere to the standard timing for amiodarone. The trial targets those who have experienced cardiac arrest outside a hospital and are treated by emergency medical services, provided they do not have an amiodarone allergy. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially life-saving advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

A previous study showed that amiodarone can help restart the heart in patients who experienced cardiac arrest, suggesting its usefulness in emergencies. However, potential side effects include low blood pressure, which can sometimes be serious, and issues with the heart's rhythm. Potential trial participants should discuss these risks with their doctors.

Amiodarone is already used for other heart rhythm problems, offering some reassurance about its safety. However, like any treatment, weighing both the potential benefits and risks is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Amiodarone for Cardiac Arrest trial because it explores two different timing protocols for administering amiodarone during a cardiac arrest event. The "Early Amiodarone Protocol" provides the drug earlier, right after the second defibrillator shock, which could potentially stabilize the heart faster compared to the usual timing after the third shock. This approach might offer quicker intervention during critical moments of cardiac arrest, aiming to improve survival and recovery rates. By testing these variations, the trial seeks to determine the most effective timing for amiodarone administration, which could lead to improved outcomes for patients experiencing cardiac arrest.

What evidence suggests that this modified cardiac arrest treatment protocol is effective for out-of-hospital cardiac arrest?

This trial will compare two protocols for administering amiodarone during cardiac arrest. The Early Amiodarone Protocol involves administering amiodarone after the second defibrillator shock, during the same two-minute cycle as the initial dose of epinephrine. The Usual Care Protocol administers amiodarone after the third defibrillator shock, one two-minute cycle after the initial dose of epinephrine.

Research has shown that administering amiodarone within 23 minutes of an emergency call can improve survival for patients experiencing certain types of cardiac arrest, specifically shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). One study found that patients who received amiodarone had a 44% higher chance of surviving without complications over four years compared to those who received standard treatment. However, another study found that neither amiodarone nor lidocaine significantly improved survival or brain function compared to a placebo. Despite these mixed results, the timing of amiodarone administration appears crucial for its effectiveness during cardiac arrest. ^{6 7 8 9 10}

Who Is on the Research Team?

Joshua Lupton, MD, MPH

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for individuals who have had a non-traumatic out-of-hospital cardiac arrest with an initial heart rhythm of ventricular fibrillation or tachycardia, and the condition persists after one defibrillation attempt. It's not for those with amiodarone contraindications, pre-existing 'do-not-resuscitate' orders, prisoners, pregnant women, children as determined by EMS, or known allergy to amiodarone.

Inclusion Criteria

Initial rhythm on EMS rhythm assessment of ventricular fibrillation or ventricular tachycardia

My heart condition did not improve after one defibrillation attempt.

I was treated by EMS for a sudden heart stoppage not caused by injury.

Exclusion Criteria

Known allergy to amiodarone

Pre-existing 'do-not-attempt-resuscitation' orders

Inter-facility transportations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Administration of amiodarone during cardiac arrest treatment, comparing early administration protocol to usual care

Immediate (during cardiac arrest event)

Follow-up

Participants are monitored for survival to hospital discharge and neurologically intact survival

up to 30 days

Outcome Assessment

Evaluation of secondary outcomes including adverse events and critical intervention timings

up to 1 day

What Are the Treatments Tested in This Trial?

Interventions

• Amiodarone Hydrochloride Injection

Trial Overview The study tests if giving Amiodarone Hydrochloride Injection earlier than current guidelines improves time to delivery in patients with refractory ventricular fibrillation/tachycardia during cardiac arrest. This is compared to usual care where it's given later according to existing protocols.

How Is the Trial Designed?

Group I: Early Amiodarone Protocol Experimental Treatment 1 Intervention

Amiodarone administration after the second defibrillator shock, during the same two-minute cycle as the initial dose of epinephrine.

Group II: Usual Care Protocol Active Control 1 Intervention

Amiodarone administration after the third defibrillator shock, one two-minute cycle after the initial dose of epinephrine.

Amiodarone Hydrochloride Injection is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Cordarone for:

• Life-threatening ventricular arrhythmias
• Advanced cardiac life support (ACLS) situations such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)

Approved in United States as Pacerone for:

• Life-threatening ventricular arrhythmias
• Advanced cardiac life support (ACLS) situations such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)

Approved in Canada as Amiodarone Hydrochloride for:

• Life-threatening ventricular arrhythmias
• Advanced cardiac life support (ACLS) situations such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)

Approved in European Union as Amiodarone Hydrochloride for:

• Life-threatening ventricular arrhythmias
• Advanced cardiac life support (ACLS) situations such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Amiodarone has been commonly used to manage atrial arrhythmias in patients with hypertrophic cardiomyopathy (HCM), but its effectiveness in preventing life-threatening ventricular arrhythmias is still debated.

Recent studies on implantable cardioverter defibrillators (ICDs) have prompted a reassessment of amiodarone's role in HCM management, suggesting that its use may need to be reconsidered in light of new evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of pharmacologic treatment to prevent sudden death in the implantable cardioverter defibrillator era. Elliott, PM.[2019]

In a study of 124 patients over 10 years, low-dose amiodarone therapy effectively controlled serious ventricular and supraventricular arrhythmias, achieving satisfactory arrhythmia control in 78% of patients with ventricular tachyarrhythmias at 1 year and 73% for supraventricular arrhythmias.

The incidence of adverse effects from low-dose amiodarone was low, at 5.8 per 100 patient years, suggesting that it offers a favorable safety profile compared to higher doses, with a successful treatment rate of 67% at 1 year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term low-dose amiodarone therapy in the management of ventricular and supraventricular tachyarrhythmias: efficacy and safety. Lee, KL., Tai, YT.[2020]

Amiodarone, an antiarrhythmic medication, may be linked to the development of asymptomatic bone marrow granulomas, as observed in two patients undergoing treatment.

The study highlights the need for awareness of potential adverse effects of amiodarone, given its wide range of side effects, including the formation of granulomas in bone marrow without evidence of infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone-associated granuloma in bone marrow. Rosenbaum, H., Ben-Arie, Y., Azzam, ZS., et al.[2017]

Amiodarone is a versatile anti-arrhythmic drug effective in treating ventricular tachyarrhythmias, with both oral and intravenous forms; intravenous amiodarone can provide immediate effects in life-threatening situations, such as after out-of-hospital cardiac arrest, improving survival rates to hospital admission.

In addition to its established role in ventricular tachyarrhythmias, amiodarone is also effective for atrial fibrillation and flutter, showing comparable efficacy to other anti-arrhythmic medications, making it a strong candidate for first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone -- waxed and waned and waxed again. Doggrell, SA.[2019]

Current evidence does not support the use of amiodarone for preventing sudden death in myocardial infarction survivors with depressed left ventricular function, as trials have shown no significant mortality reduction despite a 35% decrease in sudden death risk.

Amiodarone is considered safe for use in patients with left ventricular dysfunction, as it does not increase mortality, making it the preferred antiarrhythmic treatment in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone and "primary" prevention of sudden death: critical review of a decade of clinical trials. Farré, J., Romero, J., Rubio, JM., et al.[2019]

Amiodarone hydrochloride effectively controlled a recurrent supraventricular arrhythmia in a 57-year-old patient who did not respond to conventional treatments, demonstrating its efficacy in difficult cases.

The patient has been free of arrhythmia for 11 months while on amiodarone, and importantly, she has not experienced any significant side effects from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of recurrent supraventricular tachycardia with amiodarone hydrochloride. Swan, JH., Chisholm, AW.[2018]

In a study of 61 patients treated long-term with a daily dose of 400 mg of amiodarone, only 4.9% showed clinically evident pulmonary side effects, indicating a lower prevalence of lung toxicity compared to higher doses.

While most lung function values were normal, there was a slight decrease in transfer factor for carbon monoxide and exercise capacity in amiodarone patients, suggesting a small impact on lung function, with individual susceptibility playing a role in potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary complications after long term amiodarone treatment. Roca, J., Heras, M., Rodriguez-Roisin, R., et al.[2019]

Amiodarone is highly effective and safe for treating and preventing ventricular arrhythmias, especially in emergency situations like shock refractory out-of-hospital cardiac arrest.

While implantable cardioverter defibrillators (ICDs) are superior for long-term prevention of arrhythmias, amiodarone, particularly when combined with beta-blockers, is the best option for preventing ICD shocks and managing electrical storms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia. Van Herendael, H., Dorian, P.[2021]

Amiodarone is an effective antiarrhythmic medication, particularly for treating supraventricular tachycardias and potentially atrial fibrillation, but its use is limited due to a range of serious side effects affecting multiple organ systems.

The drug has a complex pharmacokinetic profile, with a long half-life that can extend up to 58 days after long-term use, necessitating careful monitoring and restriction to serious arrhythmias that do not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone: a unique antiarrhythmic agent. Sloskey, GE.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10250159/

The impact of time to amiodarone administration on ... Amiodarone administered within 23 minutes of the emergency call is associated with improved survival outcomes in shock-refractory VF/pVT.

2. ahajournals.org ahajournals.org/doi/10.1161/01.cir.100.19.2025

Evidence-Based Analysis of Amiodarone Efficacy and Safety At 4 years of follow-up, event-free survival was 52% for amiodarone and 36% for conventional care, a 44% increase.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1514204

Amiodarone, Lidocaine, or Placebo in Out-of-Hospital ... Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo.

4. journal.chestnet.org journal.chestnet.org/article/S0012-3692(22)04039-9/abstract

Comparative Effectiveness of Amiodarone and Lidocaine for ... This retrospective cohort study of adult patients receiving amiodarone or lidocaine for VT/VF in-hospital cardiac arrest refractory to CPR and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0300957225000462

Amiodarone dose in patients with shockable out-of-hospital ... The subgroup analysis revealed a consistent treatment benefit of amiodarone 300 mg over 450 mg in patients under the age of 60 years, with witnessed cardiac ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1880427613001592

Systematic review of the use of intravenous amiodarone ... Amiodarone and nifekalant were equally effective in preventing electrical storm (67% vs. 67%). The defibrillation effect for CPR was also equal in the 2 groups ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482154/

Amiodarone - StatPearls - NCBI Bookshelf - NIH In studies involving out-of-hospital cardiac arrest patients, amiodarone was associated with a higher rate of return of spontaneous circulation ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/amiodarone-intravenous-route/description/drg-20073219

Amiodarone (intravenous route) - Side effects & uses Amiodarone injection is used to treat life-threatening heart rhythm problems called ventricular arrhythmias.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/075955s015lbl.pdf

Amiodarone HCl injection for intravenous use Cardiovascular: hypotension (sometimes fatal), sinus arrest has been limited experience in patients receiving intravenous amiodarone for arrhythmia ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT06680869

Early Amiodarone in Shockable Cardiac Arrest Evaluated secondary outcomes will include the proportion of patients receiving amiodarone before their third defibrillation, pulses present at emergency ...