Cardiac Effects of Mineralocorticoid Receptor Antagonism After Preeclampsia

NCT07238400 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025P001799R01HL181150
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to determine if the medication eplerenone yields greater improvements in coronary microvascular function than chlorthalidone in women who experienced preeclampsia during pregnancy and subsequently developed chronic hypertension. The main Aims are:

• To test the hypothesis that, in women with prior preeclampsia, current chronic hypertension, and concentric LV remodeling, eplerenone improves coronary microvascular function vs. chlorthalidone.
• To test the hypothesis that, in women with prior preeclampsia, current chronic hypertension, and concentric LV remodeling, eplerenone improves cardiac structure and function vs. chlorthalidone. Participants will:
• First receive pre-treatment with Amlodipine for 12 weeks prior to beginning the study medication.
• Start study treatment which involves daily self-administration of two oral capsules (eplerenone + potassium placebo or chlorthalidone + potassium), each taken once a day, for a total of 336 doses over 48 weeks.
• Attend study visits at weeks 2, 12, 24, 36, and 48. These visits will involve collecting information, measuring blood pressure, and gathering blood and urine samples. Echocardiography (cardiac ultrasound), eye exam, and cardiac PET/CT scan will be performed during the baseline and week 48 visits.

Conditions

Hypertension

Keywords

Hypertension; Mineralocorticoid receptor; chlorthalidone; eplerenone; heart; microvascular; preeclampsia

Outcome Measures

Primary Outcomes (1)

• Change in Myocardial Flow Reserve (MFR)

  Subjects will undergo 13N cardiac PET imaging at baseline and after 48 weeks of randomized study treatment. Myocardial blood flow (MBF) will be determined during the stress and rest conditions. Myocardial flow reserve will be calculated as stress MBF divided by rest MBF.

  Prior to randomization and after 48 weeks of randomized study treatment.

Secondary Outcomes (10)

• Ratio of mitral E velocity to e' [E/e']

  Prior to randomization and after 48 weeks of randomized study treatment.

• Rest Myocardial Blood Flow (MBF)

  Prior to randomization and after 48 weeks of randomized study treatment.

• Stress Myocardial Blood Flow (MBF)

  Prior to randomization and after 48 weeks of randomized study treatment.

• Subendocardial-Specific Myocardial Flow Reserve (MFR)

  Prior to randomization and after 48 weeks of randomized study treatment.

• Relative wall thickness

  Prior to randomization and after 48 weeks of randomized study treatment.

Other Outcomes (11)

• Renal blood flow

  Prior to randomization and after 48 weeks of randomized study treatment.

• Retinal vessel density

  Prior to randomization and after 48 weeks of randomized study treatment.

• Concentration of High-sensitivity cardiac troponin I

  Prior to randomization and after 48 weeks of randomized study treatment.

Study Arms (2)

Eplerenone

ACTIVE COMPARATOR

Participants will receive eplerenone 100 mg daily plus potassium placebo for 48 weeks

Drug: Eplerenone 100 mg daily; Drug: Potassium Placebo

Chlorthalidone

ACTIVE COMPARATOR

Participants will receive chlorthalidone 25 mg plus potassium 20 mEq daily for 48 weeks

Drug: Chlorthalidone 25 mg daily; Drug: Potassium Chloride

Interventions

Eplerenone 100 mg daily DRUG

Participants with a history of preeclampsia and current chronic hypertension will receive 100mg capsules of eplerenone to self-administer daily over the 48-week duration of the study treatment.

Eplerenone

Chlorthalidone 25 mg daily DRUG

Participants with a history of preeclampsia with current chronic hypertension will receive 25mg capsules of chlorthalidone to self-administer daily over the 48-week duration of the study treatment.

Chlorthalidone

Potassium Placebo DRUG

Participants taking eplerenone will also take a potassium placebo to self-administer daily over the 48-week duration of the study treatment.

Eplerenone

Potassium Chloride DRUG

Participants taking chlorthalidone will also take 20 mEq of potassium to self-administer daily over the 48-week duration of the study treatment.

Chlorthalidone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female with a history of preeclampsia (defined by ACOG criteria) in a singleton pregnancy without pre-gestational chronic hypertension.
• Current chronic hypertension (stage 1 or greater).
• Evidence of concentric left ventricular (LV) remodeling, defined as relative LV wall thickness \>0.42, with or without LV hypertrophy.
• Age 18-55 years at time of randomization.

You may not qualify if:

• Use of a mineralocorticoid receptor antagonist (MRA) or amiloride within the past 3 months or more than 30 days within the previous 12 months.
• Planned pregnancy, current pregnancy, or lactation.
• Systolic BP \>150 mmHg and/or diastolic BP \>95 mmHg while on antihypertensives, or systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg if untreated.
• BMI \>45 kg/m².
• Clinical atherosclerotic cardiovascular disease, including coronary, cerebrovascular, or peripheral artery disease.
• Diabetes mellitus.
• LV ejection fraction \<40% or history of clinical heart failure (reduced or preserved ejection fraction).
• Hypertrophic or other genetic cardiomyopathy.
• Any moderate or greater valvular heart disease.
• eGFR \<60 mL/min/1.73 m².
• Urine microalbumin/creatinine ratio \>300 mg/g at screening.
• Abnormal electrolytes, hemoglobin, liver function tests, or TSH at screening or baseline.
• Plasma renin activity \<1 mg/mL/hour and aldosterone \>20 ng/dL (suggestive of primary aldosteronism).
• Use of oral contraceptives, progestin depot or implant (note: progestin-containing IUD is permitted), or menopausal hormone therapy.
• History of hypersensitivity or intolerance to calcium channel blockers, thiazides, or MRAs.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Brigham and Women's Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Hypertension; Pre-Eclampsia

Interventions

Eplerenone; Chlorthalidone; Potassium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Study Officials

• Michael Honigberg, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Murillo, MSc

CONTACT

860-336-6097; smurillo2@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Investigator, Assistant Professor

Model Details: This study is a prospective, randomized, double-blind, active comparator clinical trial.

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: November 20, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): March 16, 2029
• Study Completion (Estimated): March 30, 2029
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)