Aldosterone Antagonist Therapy for Atrial Fibrillation

Overseen By Julia Daugherty

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Piedmont Healthcare

Must not be taking: Amiodarone, Aldosterone antagonists

Disqualifiers: Atrial fibrillation, Severe renal disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-ablation

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking an aldosterone antagonist or have used amiodarone in the past 3 months.

What data supports the effectiveness of the drug spironolactone for atrial fibrillation?

Research suggests that spironolactone, an aldosterone antagonist, may help reduce episodes of atrial fibrillation by affecting the heart's structure and hormone levels. In a study, patients with recurrent atrial fibrillation who took spironolactone experienced fewer symptomatic episodes, indicating its potential benefit in managing this condition. ^{1 2 3 4 5}

Is spironolactone generally safe for humans?

Spironolactone is generally considered safe for humans, but it may have some side effects like affecting hormone levels and increasing potassium levels in the blood. It has been used safely in humans and animals for conditions like heart failure, but monitoring by a healthcare provider is important. ^{6 7 8 9 10}

How does the drug spironolactone differ from other treatments for atrial fibrillation?

Spironolactone is unique because it blocks mineralocorticoid receptors, reducing fibrosis in the heart, which may help manage atrial fibrillation. Unlike other treatments, it also has diuretic effects that help with fluid balance, and it is being explored for its potential benefits in atrial fibrillation due to its antifibrotic properties. ^{1 4 9 11 12}

What is the purpose of this trial?

This trial is testing if adding spironolactone to usual care can prevent new heart rhythm problems in patients with atrial flutter who have high blood pressure or heart failure. Spironolactone has been shown to reduce arrhythmias and maintain magnesium balance in patients with congestive heart failure.

Research Team

Bruce Stambler, MD

Principal Investigator

Piedmont Healthcare

Eligibility Criteria

This trial is for adults with a history of hypertension or heart failure, who have had atrial flutter confirmed by ECG and are scheduled for catheter ablation. They must not have any record of atrial fibrillation, severe kidney issues, hyperkalemia, or be on certain heart medications. Pregnant women and those unwilling to use birth control while taking spironolactone cannot participate.

Inclusion Criteria

You have been diagnosed with typical atrial flutter confirmed by a 12-lead ECG.

You do not have a documented irregular heart rhythm on any heart monitoring tests.

I have a history of high blood pressure or heart failure.

Exclusion Criteria

Your blood potassium level is too high.

I need a specific heart medication for another health issue.

My kidney function is severely impaired.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo CTI ablation and are randomized to receive either standard therapy or spironolactone

Immediate post-ablation

Follow-up

Participants are monitored for new-onset AF using an implantable rhythm monitor

24 months

Treatment Details

Interventions

• No Spironolactone
• Spironolactone

Trial Overview The study aims to see if the drug spironolactone can prevent new cases of atrial fibrillation after treating atrial flutter with ablation. Participants will either receive spironolactone or standard medical therapy without it, monitored long-term via an implantable rhythm device.

Participant Groups

Group I: Interventional Therapy Experimental Treatment 1 Intervention

subjects treated with an aldosterone antagonist after CTI ablation

Group II: Standard Therapy Active Control 1 Intervention

subjects undergoing CTI ablation

Who Is Running the Clinical Trial?

Piedmont Healthcare

Lead Sponsor

Trials

23

Recruited

5,700+

Findings from Research

Spironolactone (SP) encapsulated in nanostructured lipid carriers (NLCs) showed improved cell viability in rat heart cells (H9C2) at a concentration of 25 μM, while free SP was cytotoxic at the same concentration.

The study suggests that SP-NLCs can enhance cardiac tissue regeneration due to their sustained release profile, making them a promising approach for cardiac remodeling therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabrication and Evaluation of Spironolactone-Loaded Nanostructured Lipid Carries for Cardiac Tissue Regeneration. Falak, M., Mehdikhani, M., Varshosaz, J., et al.[2022]

SC 23992 is a new spirolactone that shows two to eight times greater potency as an anti-aldosterone agent in vivo compared to Aldactone, although it has only about 10% potency in vitro.

This new compound may offer a safer alternative for patients, as it appears to have fewer antiandrogen side effects compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SC 23992: radioreceptor assays for therapeutic and side effects. Funder, JW., Mercer, J., Hood, J.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

Aldosterone antagonists in hypertension and heart failure. [2022]

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

Effect of combined spironolactone-β-blocker ± enalapril treatment on occurrence of symptomatic atrial fibrillation episodes in patients with a history of paroxysmal atrial fibrillation (SPIR-AF study). [2013]

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

Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. [2016]

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

Effect of spironolactone on patients with atrial fibrillation and structural heart disease. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Effects of perindopril and spirolactone on plasma aldosterone and left atrial remodeling in a canine model of atrial fibrillation]. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The SEISICAT study: a pilot study assessing efficacy and safety of spironolactone in cats with congestive heart failure secondary to cardiomyopathy. [2018]

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

Effects of mineralocorticoid receptor antagonists on sex hormones and body composition in patients with primary aldosteronism. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Fabrication and Evaluation of Spironolactone-Loaded Nanostructured Lipid Carries for Cardiac Tissue Regeneration. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

The renal action of spirorenone and other 6 beta,7 beta; 15 beta,16 beta-dimethylene-17-spirolactones, a new type of steroidal aldosterone antagonists. [2014]

10. England pubmed.ncbi.nlm.nih.gov

SC 23992: radioreceptor assays for therapeutic and side effects. [2019]

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

Aldosterone and volume management in hypertensive heart disease. [2018]

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

Aldosterone and aldosterone antagonism in systemic hypertension. [2019]