Amiodarone for Atrial Fibrillation

(RADICAL Trial)

Overseen By Amy Banfield, MA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Kevin W Hatton, MD, PhD

Disqualifiers: Atrial fibrillation, Heart abnormalities, Respiratory disease, Liver disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how different dosing schedules of amiodarone, a medication for irregular heartbeats, work for patients who develop atrial fibrillation after non-emergency heart surgery. The study compares two methods: one with repeated doses when the heart rate increases and another with a conventional dosing schedule. It seeks participants planning to undergo heart surgery, such as a bypass or valve repair, who have not experienced previous irregular heartbeats or certain heart procedures. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for amiodarone?

Studies have shown that amiodarone is generally well-tolerated, even in large doses. Research indicates that a 150 mg dose administered directly into a vein (IV) is safe, but higher daily doses can increase the risk of side effects like low blood pressure.

For repeated doses, additional 150 mg IV doses are sometimes used to manage fast heart rates, and available data considers these safe. However, larger doses can raise the risk of side effects.

In the usual treatment plan, similar safety findings apply. This plan typically starts with a 150 mg IV dose, followed by a continuous drip. This approach aims to control heart rhythms effectively while maintaining safety. Both dosing methods have been studied, and while generally safe, healthcare providers must closely monitor for any potential side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the repeated amiodarone dosing regimen (RBDR) because it offers a proactive way to manage tachycardia during cardiac surgeries. Unlike conventional dosing, which follows a set schedule, the RBDR allows for additional amiodarone boluses whenever a patient's heart rate spikes above 110 beats per minute for more than 10 minutes. This approach aims to provide more immediate control over heart rate fluctuations, potentially improving patient outcomes in a high-stakes surgical setting.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation after cardiac surgery?

Research has shown that amiodarone helps control irregular heartbeats after heart surgery. One study found that 72% of patients with frequent irregular heartbeats experienced complete cessation of these episodes with amiodarone. In this trial, participants will receive one of two dosing regimens. The conventional dosing regimen effectively controls and maintains a normal heart rate. The repeated bolus dosing regimen, which involves administering extra doses when the heart rate spikes, might offer additional benefits. Both methods aim to reach a total of 8 grams of amiodarone, and studies suggest they are equally effective in managing heart rate issues after surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

Kevin Hatton, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

Inclusion Criteria

Subject must undergo or scheduled for non-emergent cardiac surgery, including coronary artery bypass grafting (CABG), non-infectious valve repair or replacement, atrial or septal defect repair, thoracic aortic replacement surgery, or any combination of these procedures

Subject must be willing to give written informed consent

Exclusion Criteria

You have a history of heart rhythm issues.

You have had a heart procedure in the past that affected your heart's electrical system.

Low cardiac index or cardiogenic shock requiring pharmacologic or mechanical support

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a conventional or repeated amiodarone dosing regimen to manage postoperative atrial fibrillation

24 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart rate and rhythm stability

up to 20 days

Regular monitoring during ICU and hospital stay

Long-term follow-up

Participants are monitored for recurrent atrial fibrillation and maintenance of normal sinus rhythm until hospital discharge

up to 20 days

What Are the Treatments Tested in This Trial?

Interventions

• Amiodarone

How Is the Trial Designed?

Group I: Repeated amiodarone bolus dosing regimen (RBDR) Active Control 1 Intervention

Initial amiodarone bolus of 150 mg IV over 10 minutes, then 1.0 mg/min IV amiodarone infusion for 6 hours, then a 0.5 mg/min IV amiodarone infusion for 18 hours, followed by enteral (400 mg amiodarone oral or per tube three times daily or 2 times daily if the patient has gastrointestinal intolerance when taking the drug three times daily) or intravenous amiodarone (0.5 mg/min continuous infusion) to complete an 8-gm total amiodarone load. In addition, patients in the RBDR will receive an additional 150 mg IV amiodarone bolus whenever the patient develops tachycardia (Heart Rate (HR) = 110 beats per minute) lasting more than 10 minutes. This bolus may be repeated up to a total of 5 times (6 total boluses) over the first 24 hours. Maintenance amiodarone (200 mg amiodarone oral or per tube once daily) at discretion of attending physician.

Group II: Conventional amiodarone dosing regimen (CDR) Active Control 1 Intervention

Initial amiodarone bolus of 150 mg IV over 10 minutes then a 24-hour amiodarone loading infusion (1 mg/min for 6 hours followed by 0.5 mg/min for 18 hours), followed by enteral (400 mg amiodarone oral or per tube three times daily or 2 times daily if the patient has gastrointestinal intolerance when taking the drug three times daily) or intravenous amiodarone (0.5 mg/min continuous infusion) to complete an 8-gm total amiodarone load. Maintenance amiodarone (200 mg amiodarone oral or per tube once daily) at discretion of attending physician.

Who Is Running the Clinical Trial?

Kevin W Hatton, MD, PhD

Lead Sponsor

Trials

1

Recruited

3+

Kevin Hatton

Lead Sponsor

Trials

2

Recruited

4+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8227846/

Prospective, randomized comparison of conventional and ... The therapeutic and electrophysiologic effects of conventional and high dose loading regimens of amiodarone do not differ significantly after 3 or 10 days ...

2. jacc.org jacc.org/doi/10.1016/0735-1097%2893%2990603-X

Prospective, randomized comparison of conventional and ... After 10 days of therapy, four patients in each group had an adequate response to amiodarone (p = NS). Three patients who received the high dose and one patient ...

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

Evidence-Based Analysis of Amiodarone Efficacy and Safety For low-dose amiodarone, high-dose amiodarone, and bretylium, these rates were 1.68, 0.48, and 0.96 events per 24 hours, respectively (P=0.237). There was no ...

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

Amiodarone - StatPearls - NCBI Bookshelf - NIH Amiodarone has demonstrated effective control of the ventricular rate and successful conversion to and maintenance of sinus rhythm in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/073510979390603X/pdf?md5=a41e485557bff43248ce9880bc43b9e1&pid=1-s2.0-073510979390603X-main.pdf

JACC Vol. 22, No. 6 The two dosing regimens we tested resulted in significant prolonga- tion of the sinus cycle length, ventricular effective refractory period and AV block cycle ...

6. drugs.com drugs.com/dosage/amiodarone.html

Amiodarone Dosage Guide + Max Dose, Adjustments Detailed Amiodarone dosage information for adults. Includes dosages for Arrhythmias; plus renal, liver and dialysis adjustments.

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

Amiodarone HCl injection for intravenous use Pediatric use: The safety and efficacy of amiodarone in the pediatric rates of infusion provided in DOSAGE AND ADMINISTRATION (2)reflect dosing in.

8. medcentral.com medcentral.com/drugs/monograph/4521-387009/amiodarone-oral

Amiodarone: uses, dosing, warnings, adverse events, ... In one study, the time to first episode of ventricular tachycardia or ventricular fibrillation was approximately 10 or 14 hours in patients receiving the 125- ...