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

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Amiodarone Hydrochloride Injection for cardiac arrest?

Amiodarone is effective in treating life-threatening heart rhythm problems, like ventricular arrhythmias, and can help improve survival to hospital admission after cardiac arrest. It is considered the most effective drug for resuscitation in cases of shock-resistant out-of-hospital cardiac arrest. ^{1 2 3 4 5}

Is amiodarone generally safe for humans?

Amiodarone has been used to treat heart rhythm problems, but it can cause serious side effects affecting the lungs, thyroid, liver, eyes, skin, and nerves. While it can be effective, its use is often limited to serious cases due to these potential risks. ^{1 2 6 7 8}

How does the drug amiodarone differ from other treatments for cardiac arrest?

Amiodarone is unique because it acts on multiple pathways in the heart, making it effective for various types of arrhythmias (irregular heartbeats). It can be administered intravenously for immediate effect in life-threatening situations, unlike some other treatments that take longer to work. ^{1 2 4 5 9}

Research Team

Joshua Lupton, MD, MPH

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

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

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

My heart condition did not improve after one defibrillation attempt.

Exclusion Criteria

Known allergy to amiodarone

My first emergency care was provided by a qualified team not in this study.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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, 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. Canada pubmed.ncbi.nlm.nih.gov

Control of recurrent supraventricular tachycardia with amiodarone hydrochloride. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Amiodarone and "primary" prevention of sudden death: critical review of a decade of clinical trials. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Amiodarone -- waxed and waned and waxed again. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Amiodarone: a unique antiarrhythmic agent. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Pulmonary complications after long term amiodarone treatment. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Amiodarone-associated granuloma in bone marrow. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

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