Cardiac Effects of Mineralocorticoid Receptor Antagonism After Preeclampsia (CARDAMOM)

July 9, 2026 updated by: Michael C. Honigberg, Massachusetts General Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Preeclampsia, a condition marked by hypertension and systemic endothelial/microvascular dysfunction in late pregnancy, affects 8% of childbearing U.S. women and is associated with two-fold risk of future material cardiovascular disease (CVD). The American College of Cardiology and American Heart Association now recognize preeclampsia as a sex-specific CVD risk factor to guide prescription of preventive statin therapy. Beyond this focused recommendation, however, specific strategies for CVD risk reduction in women with preeclampsia are not yet established. Recent preclinical evidence suggests that preeclampsia induces vascular smooth muscle cell mineralocorticoid receptor (MR) sensitivity that persists postpartum, promoting hypertension and CVD. Although MR signaling is known to underlie hypertension, MR activation also promotes cardiovascular, kidney, and metabolic disease via effects that are partially independent of blood pressure. Work by this team has implicated MR signaling in coronary microvascular dysfunction, a known predictor of heart failure with preserved ejection fraction (HFpEF) and CVD mortality. The central hypothesis is that, among women with prior preeclampsia who subsequently develop chronic hypertension, MR blockade will promote favorable cardiac remodeling and improve coronary microvascular function, independent of changes in blood pressure, and thereby reduce CVD risk in affected women. To test this hypothesis, the investigators propose a randomized, double-blind clinical study in humans. Women aged <55 years with a history of preeclampsia, current chronic hypertension, and concentric left ventricular remodeling will be randomized 1:1 to receive eplerenone (mineralocorticoid receptor antagonist) or chlorthalidone (thiazide-like diuretic) with potassium supplementation for 48 weeks, targeting equivalent blood pressure control in both groups using daily home blood pressure measurement and 24-hour ambulatory blood pressure monitoring. The investigators will measure coronary microvascular function (myocardial flow reserve, i.e., hyperemic stress/rest myocardial blood flow) quantified by cardiac positron emission tomography (PET/CT) and cardiac structure and function by cardiac ultrasound at baseline and 48 weeks. It is expected that, compared with chlorthalidone, eplerenone will yield greater improvements in coronary microvascular function and myocardial diastolic function after 48 weeks of treatment. If the hypotheses are affirmed, these findings would support the targeted use of MR antagonists much earlier than recommended by current guidelines for the management of hypertension to more effectively prevent HFpEF and other CVD among women with a history of preeclampsia.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Massachusetts General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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 18-65 years at time of randomization.

Exclusion Criteria:

  • 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.
  • Active substance abuse.
  • Other serious medical illnesses or concerns about protocol adherence/mortality risk within 15 months.
  • Participation in another interventional clinical study.
  • Participants using GLP-1 receptor agonists (GLP-1RA) are eligible only if they have received continuous treatment with the same GLP-1RA agent at an unchanged maintenance dose for ≥12 months prior to enrollment. Dose changes, agent switches, or formulation changes within the 12 months preceding enrollment are not permitted. Temporary interruptions of ≤4 consecutive weeks (e.g., due to supply issues or procedural holds) are allowed, provided the same agent and dose are resumed. At the time of enrollment, there must be no planned or anticipated GLP-1RA dose escalation, dose reduction, or discontinuation. Initiation of GLP-1RA therapy after randomization is not permitted. Dose changes during follow-up are discouraged unless clinically required.
  • Use of allopurinol.
  • Use of lithium.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Eplerenone
Participants will receive eplerenone 100 mg daily plus potassium placebo for 48 weeks
Drug: Eplerenone 100 mg daily
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.
Drug: Potassium Placebo
Participants taking eplerenone will also take a potassium placebo to self-administer daily over the 48-week duration of the study treatment.
Active Comparator: Chlorthalidone
Participants will receive chlorthalidone 25 mg plus potassium 20 mEq daily for 48 weeks
Drug: Chlorthalidone 25 mg daily
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.
Drug: Potassium Chloride
Participants taking chlorthalidone will also take 20 mEq of potassium to self-administer daily over the 48-week duration of the study treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Myocardial Flow Reserve (MFR)
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ratio of mitral E velocity to e' [E/e']
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
E/e', a measure of diastolic function, will be measured by transthoracic echocardiography.
Prior to randomization and after 48 weeks of randomized study treatment.
Rest Myocardial Blood Flow (MBF)
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
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.
Prior to randomization and after 48 weeks of randomized study treatment.
Stress Myocardial Blood Flow (MBF)
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
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.
Prior to randomization and after 48 weeks of randomized study treatment.
Subendocardial-Specific Myocardial Flow Reserve (MFR)
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
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. Subendocardial layer-specific MBF will be calculated using QPET software (Cedars-Sinai Medical Center, Los Angeles, CA). Myocardial flow reserve will be calculated as stress MBF divided by rest MBF.
Prior to randomization and after 48 weeks of randomized study treatment.
Relative wall thickness
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Relative wall thickness is calculated as 2*posterior wall thickness/LV end-diastolic diameter as measured by transthoracic echocardiography.
Prior to randomization and after 48 weeks of randomized study treatment.
Early diastolic septal mitral annular velocity [septal e']
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Septal e', a measure of diastolic function, will be measured by transthoracic echocardiography using tissue Doppler.
Prior to randomization and after 48 weeks of randomized study treatment.
Peak tricuspid regurgitant velocity
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Peak tricuspid regurgitant jet velocity, a measure of diastolic function, will be measured by transthoracic echocardiography using continuous wave Doppler.
Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial volume index
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial volume index will be measured by transthoracic echocardiogarphy using the biplane method and indexed for body surface area.
Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial reservoir strain
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial strain, a sensitive measure of end-diastolic pressure and atrial remodeling, will be quantified using TOMTEC.
Prior to randomization and after 48 weeks of randomized study treatment.
Peak global longitudinal strain
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Left ventricular global longitudinal strain, a measure of subclinical cardiac dysfunction, will be quantified using TOMTEC.
Prior to randomization and after 48 weeks of randomized study treatment.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Renal blood flow
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Renal blood flow is calculated from 13N cardiac PET images. Rest and stress renal blood flow are estimated by fitting the tissue time-activity curves to a 2-compartment kinetic model.
Prior to randomization and after 48 weeks of randomized study treatment.
Retinal vessel density
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
For OCT ocular retinal imaging, subjects will be scanned on the commercially available spectral domain OCT machine (AngioVue OCTA, RTVue, Optovue Inc., Fremont, CA). Ocular imaging will include the 3 main retinal parameters available with the latest software package: (1) foveal avascular zone size, (2) peripapillary vessel density and internal limiting membrane-nerve fiber layer thickness, and (3) macular vessel density and macular internal limiting membrane-inner plexiform layer thickness and macular internal limiting membrane-retinal pigment epithelium full retinal thickness.
Prior to randomization and after 48 weeks of randomized study treatment.
High-sensitivity C-reactive protein
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
We will measure high-sensitivity C-reactive protein, a marker of inflammation and cardiovascular disease risk, via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Urine microalbumin-to-creatinine ratio
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Microalbumin-to-creatinine will be measured through urine.
Prior to randomization and after 48 weeks of randomized study treatment.
24-hour ambulatory blood pressure
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
24-hour BP monitoring will be performed as part of the baseline and post-treatment assessments using a validated ambulatory BP monitor (WatchBP O3, microlife, Clearwater, FL). Mean 24- hour systolic and diastolic BP will be calculated from the device data.
Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of High-sensitivity cardiac troponin I
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
High-sensitivity cardiac troponin I, a marker of cardiovascular injury and remodeling, will be measured via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Level of N-terminal pro-B-type natriuretic peptide
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
NT-proBNP, a marker of cardiac wall stretch and remodeling, will be measured via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Level of Interleukin-6
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
IL-6, a marker of inflammation and cardiovascular disease risk, will be measured via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of Transforming growth factor-beta1
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
TGF-B1, a marker of fibrosis, will be measured via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of procollagen type I carboxy-terminal propeptide
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
PICP, a marker of fibrosis, will be measured via blood collection.
Prior to randomization and after 48 weeks of randomized study treatment.
Score of Coronary artery calcium
Time Frame: Prior to randomization and after 48 weeks of randomized study treatment.
Gated CT will be performed with cardiac PET scans. Coronary artery calcium scores will be quantified using the Agatston method and can range from 0 (no plaque) to more than 1000 (extensive plaque).
Prior to randomization and after 48 weeks of randomized study treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Honigberg, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 16, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025P001799
  • R01HL181150 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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