Recruiting
Phase 2

Eplerenone vs. Chlorthalidone

Sponsor:

Massachusetts General Hospital

Code:

NCT07238400

Conditions

Hypertension

Eligibility Criteria

Sex: Female

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Eplerenone 100 mg daily

Chlorthalidone 25 mg daily

Potassium Placebo

Potassium Chloride

Study Details

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

Study ID

NCT07238400

Start date

Mar 20, 2026

Status verified date

Jul, 2026

Completion date

Mar 30, 2029

Anticipated

Primary completion date

Mar 16, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 65

Healthy Volunteers: Not accepted

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 Design

Enrollment

90 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Eplerenone

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

active comparator: Chlorthalidone

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

Interventions

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.

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.

Potassium Placebo

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

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.

Primary outcome measure

  • Change in Myocardial Flow Reserve (MFR) [ Time Frame: Prior to randomization and after 48 weeks of randomized study treatment. ]

Central Contacts and Locations

Central contacts

Pearl Lee, MSc

617-721-7783plee23@mgh.harvard.edu

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Ellen Seely, MD

617-732-5666ESEELY@bwh.harvard.edu

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Pearl Lee, MSc

617-721-7783plee23@mgh.harvard.edu

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Jul 10, 2026

Last verified

Jul, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-07-10.