Eplerenone for High Blood Pressure

Overseen By Gail K Adler, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must not be taking: MR antagonists, Amiloride

Disqualifiers: Uncontrolled diabetes, Renal disease, Hepatic disease, 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: 1

Duration: 9 months

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators' goal is to show that in hypertensive men and women with left ventricular hypertrophy (LVH) treatment with a mineralocorticoid receptor (MR) antagonist, versus a thiazide-like diuretic, will improve coronary microvascular function and cardiac efficiency, which will associate with improvements in LV structure and function. The investigators will achieve this through a randomized, controlled, basic experimental study involving humans (BESH).

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, but you cannot have used MR antagonists or amiloride in the past year. You can participate if you have treated hypothyroidism or controlled diabetes with diet, exercise, or metformin.

What data supports the idea that Eplerenone for High Blood Pressure is an effective drug?

The available research shows that Eplerenone is effective in lowering blood pressure. In studies, Eplerenone reduced blood pressure significantly compared to a placebo. It was found to lower blood pressure by 50 to 75% as much as another drug called spironolactone. Eplerenone also showed a greater reduction in blood pressure compared to losartan, and it was as effective as amlodipine but better tolerated. This suggests that Eplerenone is a good option for treating high blood pressure. ^{1 2 3 4 5}

What safety data is available for eplerenone in treating high blood pressure?

Eplerenone, a selective mineralocorticoid receptor antagonist, has been studied for its safety and efficacy in treating hypertension. It is generally well tolerated, with hyperkalemia being the most common adverse event. In a postmarketing surveillance study in Japan involving 3,166 patients, the incidence of adverse drug reactions was 2.4%, with hyperkalemia occurring in 0.6% of patients. Other adverse reactions included dizziness, renal impairment, and increased serum potassium. The study confirmed eplerenone's clinically significant antihypertensive effect, with no significant new safety concerns. ^{1 2 4 6 7}

Is the drug Eplerenone (Inspra) a promising treatment for high blood pressure?

Yes, Eplerenone (Inspra) is a promising drug for high blood pressure. It helps lower blood pressure in patients who don't respond well to other treatments. It is also approved in many countries for managing hypertension, showing its effectiveness and safety. ^{1 2 3 4 6}

Research Team

Gail K Adler, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for men and women with high blood pressure and left ventricular hypertrophy (LVH), which means their heart's pumping chamber has thickened walls. Participants should have a history of hypertension but not severe illnesses like uncontrolled diabetes, serious heart failure, or recent major cardiovascular events. They must be between 18 to 70 years old and cannot be on certain medications like MR antagonists recently.

Inclusion Criteria

I have a history of high blood pressure.

My heart's muscle mass is above the normal range.

My heart's left ventricle mass index is over 110 g/m2.

Exclusion Criteria

I have had high blood pressure caused by another condition.

Your blood tests show abnormal levels of electrolytes, liver enzymes, or thyroid hormone.

I experience significant drops in blood pressure when standing up.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

Participants are transitioned to enalapril and weaned off other anti-hypertensives

2 weeks

1 visit (in-person)

Treatment

Participants receive randomized treatment with eplerenone or chlorthalidone + potassium, with dose adjustments and potential addition of amlodipine

9 months

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Chlorthalidone
• Eplerenone

Trial Overview The study tests if Eplerenone (a drug blocking certain hormone receptors) is better than Chlorthalidone (a diuretic) at improving heart vessel function and efficiency in people with LVH due to high blood pressure. It's a randomized controlled trial where participants are assigned by chance to one of the treatments.

Participant Groups

Group I: Eplerenone Active Control 1 Intervention

Participants be placed on enalapril 10 mg and weaned off their other anti-hypertensives prior to the Pre-Treatment Assessment. Amlodipine (5 to 10 mg) will be added if needed to control blood pressure. After the Pre-Treatment Assessment, participants randomized to this arm will receive 50 mg eplerenone . At 2 weeks, eplerenone will be increased to 100 mg. Amlodipine (5 to 10 mg) will be added at 6 weeks or later if needed to achieve the BP target of \<135/85 mmHg.

Group II: Chlorthalidone + potassium Active Control 2 Interventions

Participants be placed on enalapril 10 mg and weaned off their other anti-hypertensives prior to the Pre-Treatment Assessment. Amlodipine (5 to 10 mg) will be added if needed to control blood pressure. After the Pre-Treatment Assessment, participants randomized to this arm will receive 12.5 mg chlorthalidone + 10 mEq potassium. At 2 weeks, chlorthalidone will be increased to 25 mg + 20 mEq potassium. Amlodipine (5 to 10 mg) will be added at 6 weeks or later if needed to achieve the BP target of \<135/85 mmHg.

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, at doses of 50 mg and 100 mg daily, significantly reduced both systolic and diastolic blood pressure in patients with mild-to-moderate hypertension compared to placebo and other antihypertensive agents, based on a pooled analysis of 2,698 patients from 11 Phase III studies.

The treatment was well tolerated, with headache being the most common side effect, and severe hyperkalemia occurred at very low rates (up to 0.4%), indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses. Fernet, M., Beckerman, B., Abreu, P., et al.[2022]

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]

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, 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 is an effective antihypertensive agent, showing a dose-dependent reduction in blood pressure in over 3500 hypertensive patients across 11 randomized clinical trials, and is better tolerated than spironolactone.

Eplerenone not only effectively lowers blood pressure compared to placebo but also demonstrates comparable efficacy to amlodipine while being better tolerated, suggesting it should be more widely used for treating mild to moderate hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mineralocorticoid receptors in mild to moderate arterial hypertension. Pelliccia, F., Rosano, G., Patti, G., et al.[2018]

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]

In a study involving 3,166 patients with essential hypertension, eplerenone (Selara) demonstrated a significant reduction in blood pressure over 12 weeks, with systolic pressure decreasing from 152.1 mmHg to 134.8 mmHg and diastolic pressure from 85.8 mmHg to 77.7 mmHg.

The safety profile of eplerenone was favorable, with a low incidence of adverse drug reactions at 2.4%, primarily including hyperkalemia (0.6%) and dizziness, indicating it is a safe option for hypertension treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan. Takahashi, S., Hiramatsu, M., Hotta, S., et al.[2020]

References

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

Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mineralocorticoid receptors in mild to moderate arterial hypertension. [2018]

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

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

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

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan. [2020]