Eplerenone for Primary Aldosteronism

Overseen By Jenifer M Brown, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must be taking: Antihypertensives

Disqualifiers: History of MI, Cardiomyopathy, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well eplerenone can improve heart function in people with primary aldosteronism. In this condition, the body produces too much aldosterone, causing high blood pressure and potentially affecting the heart and kidneys. The trial aims to determine if eplerenone, which blocks this hormone, can reduce these risks. It seeks participants with high blood pressure who have been diagnosed with primary aldosteronism or are suspected of having it and have not yet started specific treatments. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how eplerenone can benefit more patients.

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

The trial does not specify if you need to stop taking your current medications. However, you must have hypertension treated with at least one antihypertensive drug to participate.

What is the safety track record for Eplerenone?

Research has shown that eplerenone is safe for people with high blood pressure and heart failure. Studies involving more than 3,000 patients found it generally well-tolerated. In these studies, eplerenone caused few serious side effects. Some participants experienced mild issues, such as changes in potassium levels or dizziness, but these were uncommon. The FDA has already approved eplerenone for treating high blood pressure and heart failure, confirming its safety. While no medication is without risks, eplerenone is considered a safe option for many people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for primary aldosteronism, which typically include mineralocorticoid receptor antagonists like spironolactone, eplerenone is unique because it offers a more selective approach. Eplerenone specifically targets the mineralocorticoid receptor without affecting other hormone receptors, potentially reducing side effects such as gynecomastia and menstrual irregularities. Researchers are excited about eplerenone because it may provide a more tolerable option for patients, especially those who experience adverse effects with current therapies. By focusing on this selectivity, eplerenone could improve adherence and quality of life for individuals managing primary aldosteronism.

What is the effectiveness track record for Eplerenone in treating primary aldosteronism?

Research has shown that eplerenone, the treatment under study in this trial, effectively treats primary aldosteronism, a condition where the body produces excess aldosterone. Eplerenone blocks this hormone, which can lower blood pressure. Studies have found that patients using eplerenone have a lower risk of heart-related issues and death from any cause compared to some other treatments. It is particularly beneficial when added to treatments that do not fully control blood pressure on their own. Eplerenone has also improved kidney function in some patients with primary aldosteronism. Overall, it has a strong track record in managing symptoms and risks associated with this condition. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This study is for adults aged 18-85 with high blood pressure treated with medication, specifically those diagnosed with Primary Aldosteronism (PA) who haven't been treated with drugs that block aldosterone. Participants must be able to fit in a PET/CT scanner and provide informed consent. People with a history of heart issues, allergy to eplerenone or spironolactone, current pregnancy, breastfeeding, or certain kidney problems cannot join.

Inclusion Criteria

I weigh less than 500 pounds and can fit into a PET/CT scanner.

I've had a heart PET scan and an echocardiogram recently.

I am taking medication for high blood pressure.

Exclusion Criteria

I have a history of heart issues, including heart attack, heart surgery, weak heart muscle, or heart transplant.

I am allergic or cannot take eplerenone or spironolactone.

Current pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnosis Confirmation

Participants without a confirmed diagnosis undergo testing to confirm primary aldosteronism

2-4 weeks

Treatment

Participants receive eplerenone treatment for 6 months, with echocardiogram and cardiac PET stress test before and after treatment

6 months

2 visits (in-person) for echocardiogram and PET stress test

Follow-up

Participants are monitored for changes in heart function and structure after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eplerenone

Trial Overview The trial is testing Eplerenone's effectiveness on heart function in individuals producing excess aldosterone. It aims to see if blocking aldosterone can improve cardiovascular health in PA patients. The study includes tests like cardiac PET scans and echocardiograms to monitor changes.

How Is the Trial Designed?

Group I: Eplerenone Treatment Experimental Treatment 1 Intervention

Eplerenone (50-100mg daily, as tolerated by blood pressure and potassium) for 6 months

Eplerenone is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Inspra for:

• Hypertension
• Heart failure

Approved in European Union as Eplerenone for:

• Hypertension
• Heart failure

Approved in Canada as Eplerenone for:

• Hypertension
• Heart failure

Approved in Japan as Eplerenone for:

• Hypertension
• Heart failure

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Eplerenone is a selective aldosterone receptor antagonist that shows promise in managing cardiovascular and renal diseases by providing protective effects on nonclassical tissues, which may reduce injury from excess aldosterone exposure.

Early clinical trials indicate that eplerenone can offer additional benefits in treating hypertension, heart failure, and nephropathy, but more long-term studies are needed to fully understand its impact on morbidity and mortality in patients with varying disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eplerenone: selective aldosterone antagonism in management of cardiovascular and renal disease. Brennan, BJ., Martin, NE.[2019]

Eplerenone, a selective aldosterone blocker, significantly improves mortality and morbidity in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction, as demonstrated in the EPHESUS trial with a well-defined patient population.

While eplerenone is generally well tolerated, it does have a higher incidence of hyperkalaemia compared to placebo, but it also results in significantly lower rates of hypokalaemia, making it a valuable addition to standard therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eplerenone : a review of its use in left ventricular systolic dysfunction and heart failure after acute myocardial infarction. Keating, GM., Plosker, GL.[2018]

Eplerenone, a highly selective aldosterone antagonist, shows improved tolerability and efficacy in treating cardiovascular disease compared to the older, nonselective spironolactone.

The advancements in eplerenone's design have led to better pharmacokinetic properties, enhancing its effectiveness and safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of aldosterone antagonists. Garthwaite, SM., McMahon, EG.[2022]

Aldosterone receptor antagonists, such as spironolactone and eplerenone, are recommended for many heart failure patients to improve treatment outcomes when used alongside ACE inhibitors or ARBs and beta-blockers.

The combination of these medications can enhance heart function and reduce symptoms in heart failure patients, highlighting the importance of a multi-drug approach in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldosterone receptor antagonists for heart failure: current status, future indications. Pitt, B., Rajagopalan, S.[2019]

In a study of 341 patients with uncontrolled hypertension on ACE-I or ARB therapy, adding eplerenone significantly reduced blood pressure by an average of -5.9 mmHg systolic and -2.4 mmHg diastolic, demonstrating its efficacy as an add-on treatment.

The study found that while eplerenone is safe and effective for lowering blood pressure, baseline levels of active plasma renin or serum aldosterone did not predict how well patients would respond to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? Prisant, LM., Krum, H., Roniker, B., et al.[2018]

In a study involving patients with hypertension due to primary aldosteronism, spironolactone was found to be significantly more effective than eplerenone in reducing diastolic blood pressure, with a mean change of -12.5 mmHg for spironolactone compared to -5.6 mmHg for eplerenone.

While both medications had similar overall rates of adverse events, spironolactone was associated with a higher incidence of specific side effects, such as male gynaecomastia (21.2% vs. 4.5%) and female mastodynia (21.1% vs. 0.0%), indicating that eplerenone may have a better safety profile regarding these particular side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. Parthasarathy, HK., Ménard, J., White, WB., et al.[2022]

Eplerenone is a selective aldosterone blocker that has shown effectiveness in treating hypertension and may have beneficial effects in conditions like heart failure and myocardial infarction, based on both animal and human studies.

The safety profile of eplerenone appears to be better than that of spironolactone, with a lower incidence of adverse effects reported, making it a promising option for patients needing aldosterone antagonism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eplerenone--a novel selective aldosterone blocker. Zillich, AJ., Carter, BL.[2018]

Eplerenone significantly reduces the risk of cardiovascular death and hospitalization for heart failure in patients with chronic systolic heart failure and mild symptoms, as demonstrated in the EMPHASIS-HF study.

The drug is generally well tolerated, with hyperkalemia being the most common side effect, while serious sexual adverse events are rare, indicating its selectivity for mineralocorticoid receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eplerenone: a review of its use in patients with chronic systolic heart failure and mild symptoms. Dhillon, S.[2021]

Eplerenone, a selective mineralocorticoid receptor antagonist, effectively reduces the harmful effects of aldosterone in conditions like hypertension and heart failure, supported by both preclinical and clinical evidence.

Compared to spironolactone, a nonselective aldosterone blocker, eplerenone has a better side-effect profile due to its selective binding to the mineralocorticoid receptor, which minimizes unwanted transcriptional activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone. Hu, X., Li, S., McMahon, EG., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23033260/

Effectiveness of eplerenone or spironolactone treatment in ... Results: GFR and UAE/Ucrea ratio significantly decreased in newly diagnosed PA patients after treatment initiation. In the second cohort, GFR ...

2. nature.com nature.com/articles/hr2015129

Comparison of eplerenone and spironolactone for the ... This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA.

3. withpower.com withpower.com/trial/phase-4-hyperaldosteronism-9-2021-734f8

Eplerenone for Primary Aldosteronism The available research shows that Eplerenone is effective in reducing blood pressure when added to other treatments that don't fully control it. In a study, ...

4. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.625457/full

Real-World Effectiveness of Mineralocorticoid Receptor ... Results: Of 30,777 patients with hypertension treated with MRAs, only 7.3% were evaluated for PA. 163 patients (123 with PA) had renin followed ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0953620521004374

Real world comparison of spironolactone and eplerenone ... Patients treated with eplerenone presented significantly lower risk of cardiovascular mortality and all-cause mortality than patients treated with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8109356/

Efficacy and Safety of the Selective Aldosterone Blocker ... The safety and efficacy of eplerenone for the treatment of essential hypertension has been demonstrated in clinical trials that included more than 3000 patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11395778/

Comparative effectiveness and safety of eplerenone and ... Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia.

8. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.124.22642

Clinical Management of Primary Aldosteronism: An Update We herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling.

9. academic.oup.com academic.oup.com/ejendo/article/193/2/297/8220347

Efficacy and safety of medical treatment of primary ... AbstractObjective. This study aims to analyze current medical management of primary aldosteronism (PA) in Spain, including doses, adverse events (AEs), and.