Amiodarone Patches for Atrial Fibrillation

(AMIOMEND Trial)

Overseen By Chief Operating Officer, Helios Cardio Inc., PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Helios Cardio Inc.

Must not be taking: Corticosteroids, Anti-inflammatories, QT prolongers, others

Disqualifiers: Pregnancy, Connective tissue diseases, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 months or until hospital discharge

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to is to test the safety of a new way to deliver a commonly used drug (amiodarone) used in heart surgery by placing a patch containing the drug directly on the heart instead of in an IV (vein). Participating subjects must be 20-85 year old males or females. Up to 80 participants having cardiac surgery at the University of Louisville will be involved in this study. The main questions this study aims to answer are: 1. Is the patch safe? 2. Does the patch lower the rate of atrial fibrillation (irregular heart rhythm) after cardiac surgery? Researchers will compare up to 3 different doses of the amiodarone patches (low, medium and high) to the usual treatment (Standard of Care) to see if there are differences (increases or decreases) in heart rhythms after cardiac surgery across study groups. Participants will be placed in one of 4 study groups: * Standard of Care (20 participants) * Low dose patch (20 participants) * Medium dose patch (20 participants) * High dose patch (20 participants) Participants will be monitored closely by their doctor(s) during the study and would: * Agree to participate after having their doctor, or a member of the team, explain the study in detail and allowing them to ask any questions they would like. * Sign an Informed Consent Form which will describe the study and tests in full. * Agree to have their doctor and his/her research team record your medical information, draw blood, and perform electrocardiograms, or EKGs (quick, painless test that measures the electrical activity of the heart) and echocardiograms (image of heart) to monitor their heart. * Agree to receive training on the portable EKG recorder and to use it at home approximately 30 days and 6 months after their surgery to monitor their heart. * Agree to return to the hospital approximately 30 days and 6 months after their surgery for a study visit. Participant involvement will be approximately 7 months total.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that interact with amiodarone, such as doxorubicin, fosphenytoin, and others listed in the exclusion criteria. If you are on these medications, you may need to stop them to participate in the trial.

What data supports the effectiveness of the Amiodarone-Infused CardiaMend Patches for treating atrial fibrillation?

Research suggests that delivering amiodarone directly to the heart through a patch can reduce the risk of atrial fibrillation while minimizing side effects, as it targets the heart specifically and avoids high drug levels in the rest of the body. ^{1 2 3 4 5}

Is Amiodarone safe for use in humans?

Amiodarone has been used successfully for many years to treat heart rhythm problems, but it can have serious side effects, especially with long-term use. A newer version, Nexterone, may have fewer side effects like low blood pressure. However, it's important to monitor for potential adverse effects when using amiodarone. ^{6 7 8 9 10}

How is the Amiodarone-Infused CardiaMend Patch treatment for atrial fibrillation different from other treatments?

The Amiodarone-Infused CardiaMend Patch is unique because it delivers the drug directly to the heart tissue, potentially reducing side effects that occur with oral or intravenous administration, which affects the whole body. ^{1 11 12 13 14}

Research Team

Mark Slaughter, MD

Principal Investigator

University of Louisville Hospitals

Eligibility Criteria

This trial is for men and women aged 20-85 undergoing cardiac surgery at the University of Louisville. They must be willing to consent to medical monitoring, blood draws, EKGs, echocardiograms, use a portable EKG recorder post-surgery, and return for follow-up visits.

Inclusion Criteria

Subjects in sinus rhythm at the time of office visit and during prior EKG (continuous EKG monitoring for 48 hours is not required)

I am between 20 and 85 years old.

Subjects able to give voluntary written informed consent, understand, and comply with study-related procedures

Exclusion Criteria

I have an active infection where my implant will be placed.

I have had heart surgery through a cut in my chest bone.

I am not pregnant, breastfeeding, have been pregnant in the last 3 months, or planning to become pregnant during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cardiac surgery and receive amiodarone-infused CardiaMend patches or standard care

Up to 2 months or until hospital discharge

In-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including use of portable EKG recorder at home

6 months

2 visits (in-person) at 30 days and 6 months post-surgery

Extension

Participants may continue to be monitored for long-term outcomes and safety

Long-term

Treatment Details

Interventions

• Amiodarone-Infused CardiaMend Patches

Trial Overview The study tests Amiodarone-Infused CardiaMend patches (70mg, 150mg & 300mg) against standard care in preventing new-onset atrial fibrillation after heart surgery. Participants are randomly assigned to one of four groups: standard care or low, medium or high dose patch.

Participant Groups

Group I: Group 4: 20 subjects receiving CardiaMend-Amiodarone infused with 300 mg of amiodarone. Experimental Treatment 1 Intervention

Subjects in Group 4 (300 mg) will receive three patches each as follows: * One patch (5x6 cm) will be placed on top of the right atrium; * One patch (3x5 cm) will be placed within the transverse sinus near the dome of the left atrium; and * One patch (3x5 cm) will be placed within the oblique sinus on the posterior/inferior aspect of left atrium

Group II: Group 3: 20 subjects receiving CardiaMend-Amiodarone infused with 150 mg of amiodarone. Experimental Treatment 1 Intervention

Subjects in Group 3 (150 mg) will receive three patches each as follows: * One patch (5x6 cm) will be placed on top of the right atrium; * One patch (3x5 cm) will be placed within the transverse sinus near the dome of the left atrium; and * One patch (3x5 cm) will be placed within the oblique sinus on the posterior/inferior aspect of left atrium

Group III: Group 2: 20 subjects receiving CardiaMend-Amiodarone infused with 70 mg of amiodarone Experimental Treatment 1 Intervention

Subjects in Group 2 (70 mg) will receive three patches each as follows: * One patch (5x6 cm) will be placed on top of the right atrium; * One patch (3x5 cm) will be placed within the transverse sinus near the dome of the left atrium; and * One patch (3x5 cm) will be placed within the oblique sinus on the posterior/inferior aspect of left atrium

Group IV: Group 1: 20 subjects in the control group, which is the standard of care (i.e., no CardiaMend-Amioda Active Control 1 Intervention

Subjects in treatment Group 1 (control) will receive no CardiaMend-Amiodarone patches.

Amiodarone-Infused CardiaMend Patches is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cordarone for:

• Ventricular arrhythmias
• Atrial fibrillation

Approved in European Union as Cordarone for:

• Ventricular arrhythmias
• Atrial fibrillation
• Tachyarrhythmias

Approved in Canada as Nexterone for:

• Ventricular arrhythmias
• Atrial fibrillation

Approved in Japan as Pacerone for:

• Ventricular arrhythmias
• Atrial fibrillation

Who Is Running the Clinical Trial?

Helios Cardio Inc.

Lead Sponsor

Trials

3

Recruited

170+

Findings from Research

The use of amiodarone-eluting epicardial patches in goats resulted in significantly higher drug concentrations in the right atrium compared to the left atrium and ventricles, while keeping plasma levels very low, which minimizes systemic side effects.

This targeted delivery method improved electrophysiological parameters, such as increasing the atrial effective refractory period and decreasing the inducibility of rapid atrial responses, suggesting it could effectively prevent postoperative atrial fibrillation with reduced risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch. Bolderman, RW., Bruin, P., Hermans, JJ., et al.[2018]

Dronedarone and vernakalant are two promising new antiarrhythmic drugs for managing atrial fibrillation (AF), with dronedarone used for chronic control and vernakalant for acute control.

While rhythm and rate control strategies for AF show no significant difference in mortality, the search for safer and more effective anti-AF agents continues, as existing antiarrhythmic drugs can have serious side effects and high hospitalization costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New anthyarrhythmic drugs for atrial fibrillation. Matassini, MV., Guerra, F., Scappini, L., et al.[2018]

Dronedarone, a drug developed to provide a safer alternative to amiodarone, has been shown to reduce mortality and hospitalization rates in patients with non-permanent atrial fibrillation (AF), making it a viable first-line therapy for maintaining sinus rhythm.

However, dronedarone is not recommended for patients with permanent AF or heart failure, as it can increase mortality and morbidity in these groups, highlighting the importance of careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation. Adlan, AM., Lip, GY.[2021]

In a study comparing amiodarone to AV node radiofrequency ablation (RFA) for chronic atrial fibrillation (AF), only 30% of patients on amiodarone maintained normal ventricular rhythm after 12 months, while RFA proved to be significantly more effective for long-term management of drug-resistant AF.

Amiodarone was generally well tolerated with minimal side effects, but the study highlights that RFA and permanent pacing are more reliable options for patients who do not respond to medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac rate normalization in chronic atrial fibrillation: comparison of long-term efficacy of treatment with amiodarone versus AV node ablation and permanent His-bundle pacing. Kirkutis, A., Poviliŭnas, A., Griciene, P., et al.[2013]

Dronedarone and vernakalant have shown promising efficacy and safety in treating atrial fibrillation, with vernakalant demonstrating superior effectiveness compared to traditional drugs like amiodarone and flecainide.

New potential antiarrhythmic drugs, including ranolazine and colchicine, are emerging, and ongoing research into selective ionic channel inhibitors and anti-inflammatory compounds may enhance long-term treatment outcomes for atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging pharmacotherapies for the treatment of atrial fibrillation. Capucci, A., Cipolletta, L., Guerra, F., et al.[2018]

Nexterone®, a new formulation of intravenous amiodarone, has been shown to be effective in managing life-threatening ventricular arrhythmias without causing hypotension, a common side effect of traditional amiodarone.

While intravenous amiodarone is effective for treating arrhythmias, studies indicate that it does not improve survival rates after cardiac events, highlighting the need for further research into antiarrhythmic drugs that can enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone (Nexterone) injection for the treatment and prophylaxis of frequently recurring ventricular fibrillation. Marinelli, A., Capucci, A.[2013]

Dronedarone is a safer alternative to amiodarone, designed to maintain normal heart rhythm with a lower risk of toxicity, making it suitable for carefully selected patients without advanced heart failure or other significant risk factors.

Clinical trials indicate that while dronedarone is moderately effective in maintaining normal sinus rhythm, it is particularly beneficial for younger patients who do not have other cardiovascular risks, helping them avoid the long-term side effects associated with more toxic anti-arrhythmic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dronedarone in the treatment of patients with atrial fibrillation. Khan, MH., Rochlani, Y., Aronow, WS.[2018]

Amiodarone has been effectively used for 14 years in Europe for managing resistant supraventricular and ventricular arrhythmias, showing its potential as a long-term treatment option.

Despite its effectiveness, amiodarone has potential side effects that have delayed its approval by the FDA, highlighting the need for careful monitoring of both its efficacy and adverse effects in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone--an investigative drug in the coronary care unit. Valladares, BK., Lemberg, L.[2013]

Dronedarone, a new antiarrhythmic drug, has shown safety and efficacy in maintaining normal heart rhythm in patients with atrial fibrillation or flutter, based on two phase III trials involving various patients.

At a dosage of 400 mg twice daily, dronedarone effectively prevented both symptomatic and asymptomatic episodes of atrial fibrillation or flutter, with a safety profile comparable to that of a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronedarone: a new antiarrhythmic agent. Zareba, KM.[2018]

Amiodarone is a well-established antiarrhythmic drug effective for various arrhythmias, including atrial fibrillation, with a low risk of serious cardiac side effects, but it has significant noncardiac adverse effects that can limit its long-term use.

Dronedarone is an investigational drug designed to mimic the cardiac benefits of amiodarone while aiming to reduce the incidence of adverse effects, as supported by various animal and human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the investigational antiarrhythmic agent dronedarone. Tafreshi, MJ., Rowles, J.[2018]

Dronedarone is an effective alternative to amiodarone for maintaining sinus rhythm in patients with atrial fibrillation, showing benefits in reducing mortality and morbidity in high-risk patients.

While dronedarone has a similar mechanism of action to amiodarone, it may pose safety risks for patients with severe heart failure, highlighting the importance of patient selection in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronedarone. Patel, C., Yan, GX., Kowey, PR.[2022]

Amiodarone is the most effective antiarrhythmic drug for controlling atrial fibrillation and can improve quality of life, but it does not reduce mortality or severe morbidity associated with the condition.

In patients with life-threatening ventricular arrhythmias, amiodarone may slightly decrease mortality, but its use requires careful monitoring due to potential adverse effects, and it can increase defibrillation thresholds in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of amiodarone in the era of the implantable cardioverter defibrillator. Dorian, P., Mangat, I.[2019]

In a study of 200 cardiac surgery patients, the use of topical amiodarone applied to the heart did not significantly reduce the incidence of new-onset atrial fibrillation (AF) compared to a control group without amiodarone.

The results showed similar rates of postoperative AF across all groups, suggesting that topical amiodarone may not be effective in preventing AF after cardiac surgery, particularly in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical amiodarone during cardiac surgery: Does epicardial application of amiodarone prevent postoperative atrial fibrillation? Greenstein, D., Beau, J., Gottlieb, G., et al.[2019]

Amiodarone is effective in reducing arrhythmic events in patients with post-myocardial infarction and congestive heart failure, but it does not significantly lower overall mortality rates, as shown in trials like EMIAT and CAMIAT.

In high-risk patients, such as those with a history of sustained ventricular tachycardia, implantable cardioverter-defibrillators (ICDs) are more effective than amiodarone in improving overall survival, indicating that while amiodarone is safe, ICDs should be prioritized for frontline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone: clinical trials. Naccarelli, GV., Wolbrette, DL., Patel, HM., et al.[2022]

References

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

Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch. [2018]

2. England pubmed.ncbi.nlm.nih.gov

New anthyarrhythmic drugs for atrial fibrillation. [2018]

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

Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation. [2021]

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

Cardiac rate normalization in chronic atrial fibrillation: comparison of long-term efficacy of treatment with amiodarone versus AV node ablation and permanent His-bundle pacing. [2013]

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

Emerging pharmacotherapies for the treatment of atrial fibrillation. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Amiodarone (Nexterone) injection for the treatment and prophylaxis of frequently recurring ventricular fibrillation. [2013]

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

Efficacy and safety of dronedarone in the treatment of patients with atrial fibrillation. [2018]

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

Amiodarone--an investigative drug in the coronary care unit. [2013]

9. Spain pubmed.ncbi.nlm.nih.gov

Dronedarone: a new antiarrhythmic agent. [2018]

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

A review of the investigational antiarrhythmic agent dronedarone. [2018]

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

Dronedarone. [2022]

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

Role of amiodarone in the era of the implantable cardioverter defibrillator. [2019]

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

Topical amiodarone during cardiac surgery: Does epicardial application of amiodarone prevent postoperative atrial fibrillation? [2019]

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

Amiodarone: clinical trials. [2022]