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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether spironolactone, an aldosterone antagonist, can prevent new cases of atrial fibrillation (an irregular heartbeat) after a procedure for atrial flutter (another heart rhythm issue). Researchers will compare spironolactone to standard care, using a small device to track heart rhythms over time. Individuals diagnosed with typical atrial flutter and who have high blood pressure or heart failure may qualify for this trial if they have not experienced atrial fibrillation before. As an Early Phase 1 trial, this research aims to understand how spironolactone works in people, offering participants a chance to contribute to groundbreaking medical insights.

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.

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

Research has shown that spironolactone is generally safe for people. However, some individuals might experience side effects. Common issues include changes in hormone levels and increased potassium in the blood. Some people have reported side effects like breast pain or swelling and allergic reactions.

Since this study is in an early phase, the main goal is to test the treatment's safety. Although spironolactone is approved for other uses, it is important to observe how participants respond to it in this specific study. Participants should discuss any concerns with their doctor before joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using spironolactone for atrial fibrillation because it offers a unique approach by targeting aldosterone, a hormone that can contribute to heart rhythm issues. Unlike standard treatments that primarily focus on controlling heart rate or rhythm directly, spironolactone works as an aldosterone antagonist, potentially addressing an underlying cause of the condition. This mechanism could not only help manage atrial fibrillation but also improve heart health overall, setting it apart from current options like beta-blockers and antiarrhythmic drugs.

What evidence suggests that spironolactone might be an effective treatment for atrial fibrillation?

Research shows that spironolactone, a drug that blocks the hormone aldosterone, might not benefit everyone with atrial fibrillation, an irregular heartbeat. Some studies have found it didn't reduce the risk of new atrial fibrillation in individuals with certain heart conditions. However, one study found that people taking spironolactone had fewer hospital visits related to atrial fibrillation than those who didn't take it. This trial will compare spironolactone with standard therapy to evaluate its effectiveness in reducing hospital stays for some people with this condition. Overall, the effectiveness of spironolactone for atrial fibrillation depends on the patient's specific health conditions. ^{1 2 5 6 7}

Who Is on the Research Team?

Bruce Stambler, MD

Principal Investigator

Piedmont Healthcare

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/JAHA.119.016239

Spironolactone in Atrial Fibrillation With Preserved Cardiac ... Spironolactone therapy did not improve peak oxygen consumption at 2 years (14.0 mL/min per kg [SD, 5.4]) compared with placebo (14.5 [5.1], ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31214914/

Effect of Spironolactone on Atrial Fibrillation in Patients ... Conclusion: Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of ...

3. evidence.nihr.ac.uk evidence.nihr.ac.uk/alert/spironolactone-not-effective-atrial-fibrillation-preserved-ejection-fraction/

Spironolactone is not an effective treatment for one type of ... People with an irregular heartbeat - atrial fibrillation – do not benefit from the drug spironolactone, according to the IMPRESS-AF trial.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02673463

NCT02673463 | Spironolactone in Atrial Fibrillation Study Overview​​ This study aims to assess whether treatment with a drug called spironolactone, which is an aldosterone inhibitor, can improve ability to cope ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21674535/

Effect of spironolactone on patients with atrial fibrillation and ... Results: Patients receiving spironolactone had significantly fewer primary outcome events (AF-related hospitalizations or DCCV) (22% vs 53%, P = 0.027).

6. withpower.com withpower.com/trial/aldosterone-antagonist-therapy-for-atrial-fibrillation-53488

Aldosterone Antagonist Therapy for Atrial Fibrillation Spironolactone is generally considered safe for humans, but it may have some side effects like affecting hormone levels and increasing potassium levels in the ...

7. researchgate.net researchgate.net/publication/344222655_Spironolactone_in_Atrial_Fibrillation_With_Preserved_Cardiac_Fraction_The_IMPRESS-AF_Trial

(PDF) Spironolactone in Atrial Fibrillation With Preserved ... Conclusions Spironolactone therapy does not improve exercise capacity, E/e' ratio, or quality of life in patients with chronic atrial fibrillation and preserved ...