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

Trial Summary

What is the purpose of this trial?

This research study aims to learn more about the impact the hormone aldosterone on the heart. Primary aldosteronism is a condition where the body's adrenal glands make too much of the hormone aldosterone, which can cause high blood pressure and increase the risk of heart and kidney disease. Treatment with medications that block aldosterone can reduce that risk. This study is trying to learn whether treatment with a medication that blocks aldosterone can improve heart function in people who make too much aldosterone.

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 data supports the idea that Eplerenone for Primary Aldosteronism is an effective treatment?

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, patients who took Eplerenone had a greater reduction in blood pressure compared to those who took a placebo. This suggests that Eplerenone can be a helpful addition for managing blood pressure in conditions like Primary Aldosteronism. Additionally, Eplerenone has been shown to improve outcomes in heart failure patients, which supports its effectiveness in managing conditions related to heart and blood pressure issues. ^{1 2 3 4 5}

What safety data is available for Eplerenone?

Eplerenone, marketed as Inspra, is a selective mineralocorticoid receptor antagonist used in various cardiovascular conditions. Safety data from clinical trials, such as EMPHASIS-HF and EPHESUS, indicate that eplerenone is generally well tolerated. The most common adverse event reported is hyperkalaemia, a known side effect of this drug class. Compared to placebo, eplerenone has a lower incidence of hypokalaemia. It has a better side-effect profile compared to nonselective aldosterone blockers like spironolactone, with fewer sexual adverse events such as gynecomastia. Overall, eplerenone is considered safe for use in heart failure and post-myocardial infarction patients, with its benefits outweighing the risks. ^{1 3 6 7 8}

Is the drug Eplerenone a promising treatment for Primary Aldosteronism?

Eplerenone is a promising drug for treating Primary Aldosteronism because it is a selective blocker that can effectively reduce high blood pressure, which is often associated with this condition. It is also known to have fewer side effects compared to similar drugs, making it a safer option for patients. ^{1 2 3 4 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

References

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

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

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

Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? [2018]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

The evolution of aldosterone antagonists. [2022]

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

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

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

Eplerenone: selective aldosterone antagonism in management of cardiovascular and renal disease. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone. [2019]

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

Eplerenone--a novel selective aldosterone blocker. [2018]

9. Netherlands 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. [2022]