Amiodarone + N-Acetylcysteine for Atrial Fibrillation

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Class Ic, Class III

Disqualifiers: AV block, Hepatic insufficiency, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding N-Acetylcysteine (NAC) to amiodarone, a medication for treating and preventing certain serious irregular heartbeats, can better prevent atrial fibrillation after major chest surgery. Researchers aim to determine if this combination reduces heart rhythm issues more effectively than amiodarone alone. Suitable candidates for this trial have a history of atrial fibrillation or face higher risk after specific chest surgeries, such as lung or esophagus operations. Participants should not have severe heart or kidney problems and must not already be on certain heart medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking class Ic or III antiarrhythmic drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amiodarone has been safely used for a long time to prevent irregular heartbeats after surgery. This medication helps control these irregular heartbeats. Studies have found that most patients tolerate amiodarone well, although some may experience side effects like nausea or a slow heart rate.

N-Acetylcysteine (NAC) often supports liver health and is considered safe when used under a doctor's guidance. Research found that using NAC with amiodarone did not increase the risk of side effects. Most patients handled the combination well, with no serious problems reported.

This trial is in a late stage, indicating that researchers have already collected extensive safety information. Previous research suggests that the combination of amiodarone and NAC is well-tolerated, with no major safety concerns noted. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for atrial fibrillation?

Unlike the standard treatments for atrial fibrillation, which typically include medications like beta-blockers, calcium channel blockers, or digoxin, the combination of Amiodarone and N-Acetylcysteine (NAC) offers a unique approach. Amiodarone is a well-known antiarrhythmic that works by affecting the electrical impulses in the heart, but when paired with NAC, it might enhance the heart's protection against oxidative stress due to NAC's antioxidant properties. Researchers are excited about this combination because it has the potential to not only regulate heart rhythm effectively but also improve overall cardiac health, offering a dual benefit that's not typical of existing treatments.

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

In this trial, participants will receive either Amiodarone with N-Acetylcysteine (NAC) or Amiodarone with a placebo. Research suggests that adding NAC to amiodarone might reduce inflammation and stress in the body, potentially preventing irregular heartbeats after surgery, known as postoperative atrial fibrillation (POAF). However, some studies found that using NAC with amiodarone did not significantly reduce the occurrence of POAF compared to amiodarone alone. The theory is that NAC could enhance the effects of amiodarone by addressing inflammation, which contributes to POAF. While promising, this theory has yielded mixed results, and further research is needed to determine if this combination is more effective than amiodarone alone. ^{1 2 3 4 6}

Who Is on the Research Team?

David Amar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having elective thoracic surgery and at high risk of post-operative atrial fibrillation (POAF). They must be stable, able to consent, in sinus rhythm, not pregnant, without severe liver or kidney issues, not on certain antiarrhythmics, and meet specific gender and biomarker criteria.

Inclusion Criteria

My breathing is stable without distress.

Patients capable of providing written, informed consent

You have a regular heartbeat.

Exclusion Criteria

My kidney function is impaired with high creatinine levels.

Known pregnancy

You are allergic to amiodarone or NAC.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amiodarone and NAC or amiodarone and placebo to prevent atrial fibrillation after thoracic surgery

7 days

Continuous monitoring in PACU

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amiodarone
• N-Acetylcysteine
• Placebo

Trial Overview The study compares two groups: one receiving amiodarone with N-Acetylcysteine (NAC), the other getting amiodarone with a placebo. It aims to see if adding NAC reduces sustained or significant POAF within 7 days after major thoracic surgery in high-risk patients.

How Is the Trial Designed?

Group I: Amiodarone + N-Acetylcysteine Experimental Treatment 2 Interventions

Amiodarone loading: 150 mg IV in PACU over one hour, then 1.0 gm/24h x 2 + NAC loading: 50 mg/kg IV in PACU over one hour, then 50 mg/kg/24h x 2 and then continuously for 48 hours.

Group II: Amiodarone + Placebo Placebo Group 2 Interventions

Amiodarone loading: 150 mg IV in PACU over one hour, then 1.0 gm/24h x 2 + NAC loading matching placebo; 50 mg/kg IV in PACU over one hour, then 50 mg/kg/24h x 2 NAC matched placebo continuously for 48 hours.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Vanderbilt University School of Medicine

Collaborator

Trials

16

Recruited

13,900+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9090984/

Amiodarone With or Without N-acetylcysteine for the ... Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and ...

2. ahajournals.org ahajournals.org/doi/10.1161/circ.142.suppl_3.14523

Abstract 14523: N-acetylcysteine for the Prevention of Atrial ... Adding N-acetylcysteine (NAC) to amiodarone may mitigate inflammation and oxidative stress, preventing postoperative atrial fibrillation (POAF).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35263434/

Amiodarone with or without N-Acetylcysteine for the ... - PubMed Conclusions: Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or ...

4. clinicaltrial.be clinicaltrial.be/en/details/10272?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Amiodarone and N-Acetylcysteine or ... This trial will be comparing the combination of amiodarone and NAC (n=122) to amiodarone alone and NAC matched placebo (n=122) to determine ...

5. withpower.com withpower.com/trial/phase-3-atrial-fibrillation-3-2016-8bd0a

Amiodarone + N-Acetylcysteine for Atrial Fibrillation This trial will be comparing the combination of amiodarone and NAC (n=122) to amiodarone alone and NAC matched placebo (n=122) to determine the rates with ...

6. cureus.com cureus.com/articles/233778-navigating-the-incidence-of-postoperative-arrhythmia-and-hospitalization-length-the-role-of-amiodarone-and-other-antiarrhythmics-in-prophylaxis

Navigating the Incidence of Postoperative Arrhythmia and ... Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively ...