Eplerenone for Preeclampsia

Overseen By Kelsey Schwartz, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Antihypertensives, Statins

Disqualifiers: Hypertension, Metabolic disease, Gestational diabetes, others

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

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug Eplerenone might improve blood vessel function in women who experienced preeclampsia during pregnancy. Preeclampsia can lead to future heart issues, and the study aims to understand and address those risks. Participants will follow a special diet to test how their blood vessels react to changes in salt intake. Women who gave birth 12 weeks to 5 years ago, experienced preeclampsia, and are not dealing with certain health conditions or medication use may be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how Eplerenone works in people, offering participants the chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you are not currently taking any antihypertensive or cholesterol-lowering medications to participate.

Is there any evidence suggesting that Eplerenone is likely to be safe for humans?

Research has shown that eplerenone is already used to treat high blood pressure in many people. It has been tested for safety in over 3,000 individuals with high blood pressure. Among these, 690 people used it for more than six months, providing substantial safety information.

Regarding pregnancy, eplerenone appears safe, with no reported issues such as changes in male fetuses, although further studies are needed for confirmation. So far, it seems well-tolerated when used for pregnancy-related conditions.

Overall, while researchers continue to study eplerenone specifically for preeclampsia, its use in other conditions offers some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about eplerenone for preeclampsia because it offers a novel approach by targeting the mineralocorticoid receptor, which is involved in blood pressure regulation. Unlike traditional treatments that primarily focus on managing symptoms, such as antihypertensives and magnesium sulfate, eplerenone works at a hormonal level, potentially addressing one of the root causes of preeclampsia. This could lead to improved outcomes by reducing blood pressure and preventing complications more effectively. Additionally, eplerenone's unique mechanism might offer a safer alternative with fewer side effects compared to current options.

What evidence suggests that Eplerenone might be an effective treatment for preeclampsia?

Research has shown that eplerenone can improve blood vessel function and lower blood pressure in conditions like preeclampsia. In animal studies, eplerenone lowered blood pressure and enhanced blood vessel health. Specifically, it helped mice with a condition similar to preeclampsia by reducing blood vessel narrowing and facilitating relaxation. Additionally, eplerenone is considered safe during pregnancy, with no reports of harm to the baby. These findings suggest that eplerenone might help manage blood vessel problems related to preeclampsia. ^{1 2 6 7 8}

Who Is on the Research Team?

Anna Reid-Stanhewicz, PhD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for women who have had preeclampsia during pregnancy and are now at risk of cardiovascular disease. It's designed to understand how their blood vessels respond to high-salt intake and if a drug can help with this issue.

Inclusion Criteria

Women who had preeclampsia and women who did not have preeclampsia

I gave birth between 3 months and 5 years ago.

Exclusion Criteria

I am taking medication to lower my cholesterol.

Body mass index less than 18.5 kg/m2

I am not allergic to the study drugs or any salt supplements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Low-salt Diet

Participants consume a low-salt diet (<2000 mg/day of sodium) for 10 days. Microvascular endothelial function is assessed on days 3 and 10.

10 days

2 visits (in-person)

High-salt Supplement

Participants consume a high-salt supplement (4500 mg/day) for 7 days while maintaining a low-salt diet. Microvascular endothelial function is assessed on day 10.

7 days

1 visit (in-person)

Follow-up

Participants are monitored for changes in microvascular endothelial function and blood pressure after the dietary interventions.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eplerenone

Trial Overview

The study tests Eplerenone, a medication that might improve how small blood vessels in the skin work after eating salt. Researchers will use a special technique to deliver the drug directly into the skin and observe changes.

How Is the Trial Designed?

Group I: High-salt supplement Experimental Treatment 1 Intervention

Participants will be counseled to consume a low-salt diet (\<2000 mg/day of sodium) for 10 days. After 3 days of a low-salt diet, participants will consume the high-salt supplement (4500 mg/day) for 7 days while maintaining a low-salt diet. On days 3 and 10, participants will arrive at the laboratory where the investigators will assess microvascular endothelial function. Blood will be collected to investigate circulating angiotensin II responses to low- (day 3) and high- (day 10) salt diet. On days 2 and 9, participants will undergo ambulatory blood pressure monitoring and 24-hour urine collection.

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Published Research Related to This Trial

Pre-eclampsia, a serious pregnancy complication characterized by high blood pressure and inflammation, significantly increases the risk of maternal and perinatal complications, but evidence-based treatments like antihypertensive therapy and magnesium sulfate can help reduce these risks.

Women who experience early-onset or severe pre-eclampsia are at a higher risk for future cardiovascular diseases, suggesting the need for ongoing monitoring of their heart health after pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The complications of hypertension in pregnancy. von Dadelszen, P., Menzies, J., Magee, LA.[2007]

A 39-year-old pregnant woman with idiopathic hyperaldosteronism (IHA) was successfully treated with esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist, after developing superimposed preeclampsia, demonstrating its potential efficacy in managing blood pressure during pregnancy.

This case highlights the safety of esaxerenone in a pregnant patient, as her blood pressure improved significantly and she delivered a healthy baby, suggesting that further research is needed to explore this treatment option for similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of a Pregnant Woman With Primary Aldosteronism and Superimposed Preeclampsia Treated With Esaxerenone. Yamashita, K., Morimoto, S., Inoue, Y., et al.[2022]

Recent large randomized trials indicate that low-dose aspirin does not significantly reduce the incidence of preeclampsia or improve perinatal outcomes, particularly in women with preexisting conditions like hypertension or diabetes.

Epidural anesthesia is considered safe for pregnant women taking low-dose aspirin, even those with severe preeclampsia, suggesting that pain management options remain viable for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What we have learned about preeclampsia. Sibai, BM., Caritis, S., Hauth, J.[2019]

Eplerenone is a selective aldosterone-receptor blocker that has a lower incidence of side effects like gynecomastia and sexual impotence compared to spironolactone, making it a safer option for patients.

Eplerenone effectively reduces high blood pressure and may be beneficial as a first-line treatment for heart failure and after myocardial infarction, especially when combined with low-dose diuretics to enhance cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The aldosterone antagonist and facultative diuretic eplerenone: a critical review. Reyes, AJ., Leary, WP., Crippa, G., et al.[2019]

Eplerenone is an effective treatment for hypertension and congestive heart failure, specifically reducing morbidity and mortality in patients with left ventricular dysfunction after a heart attack.

While eplerenone is generally safe, it can cause hyperkalemia (high potassium levels), requiring careful monitoring in patients with certain conditions like diabetes or heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical pharmacology of eplerenone. Muldowney, JA., Schoenhard, JA., Benge, CD.[2019]

Antiplatelet agents can significantly reduce the risk of pre-eclampsia by 19%, as well as lower the chances of preterm birth, stillbirth, and having a small for gestational age baby, based on a review of randomized trials.

Magnesium sulfate is highly effective in reducing the risk of eclampsia by more than half and may also lower the risk of maternal death, making it the preferred treatment for eclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-eclampsia and the hypertensive disorders of pregnancy. Duley, L.[2019]

In a study of 168 patients, treating pre-eclampsia with magnesium sulfate was found to be safe, with no cases of eclampsia reported, indicating a low risk associated with this treatment.

The duration of magnesium sulfate treatment varied significantly based on the severity of pre-eclampsia, with mild cases requiring an average of 9.5 hours compared to up to 20 hours for more severe cases, suggesting a tailored approach can enhance safety and reduce recovery time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individually determined postpartum magnesium sulfate therapy with clinical parameters to safely and cost-effectively shorten treatment for pre-eclampsia. Ascarelli, MH., Johnson, V., May, WL., et al.[2019]

Preeclampsia is diagnosed by significant increases in blood pressure after the 20th week of pregnancy, and severe cases can lead to eclampsia, which involves seizures in about 0.2% of affected patients.

Magnesium sulfate is the primary treatment for preventing and controlling seizures in preeclamptic patients, while intravenous hydralazine is preferred for managing severe hypertension; low-dose aspirin may help prevent preeclampsia in at-risk women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of preeclampsia and eclampsia. McCombs, J.[2013]

Preeclampsia is a systemic disorder that can impact multiple organ systems, requiring comprehensive evaluation and management to improve maternal and perinatal outcomes, especially when diagnosed before 34 weeks of pregnancy.

Immediate antihypertensive treatment is crucial for managing severe hypertension in preeclampsia, with specific medications recommended and certain drugs advised against, highlighting the importance of careful monitoring and tailored treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based management for preeclampsia. von Dadelszen, P., Menzies, J., Gilgoff, S., et al.[2019]

Eplerenone effectively lowers blood pressure in patients with essential hypertension, whether used alone or in combination with other medications, making it a versatile treatment option.

The drug is generally well tolerated, with manageable risks of hyperkalemia, and preliminary data suggest it may offer protective benefits against end-organ damage, although further research is needed to confirm its long-term effects on cardiovascular health and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eplerenone: a review of its use in essential hypertension. Croom, KF., Perry, CM.[2022]

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Eplerenone Reduces Blood Pressure and Improves Vascular Function in a Mouse Model of Leptin-induced Preeclampsia. Elisabeth Mellott,; Desmond ...

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Eplerenone seems to be a safe drug in pregnancy, with no reports of feminisation of male fetuses. However, more studies and data are needed to confirm these ...

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Eplerenone for Preeclampsia

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Eplerenone treatment (± esomeprazole) reduced vasoconstriction at 5-weeks postpartum and enhanced vasorelaxation at 5- and 10-weeks postpartum, ...

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Eplerenone | Circulation

This review provides an overview of the pharmacology, efficacy, and safety of a new, more selective aldosterone receptor antagonist, eplerenone.