RECRUITING Phase 2 ClinicalTrials.gov

Cardiac Effects of Mineralocorticoid Receptor Antagonism After Hypertensive Disorders of Pregnancy

Sponsor: Massachusetts General Hospital • ClinicalTrials.gov ID: NCT07238400

Registry updated: 2026-10-20

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Description

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 hypertension during pregnancy and subsequently developed chronic hypertension. The main Aims are: * To test the hypothesis that, in women with prior pregnancy-induced hypertension, current chronic hypertension, and concentric LV remodeling, eplerenone improves coronary microvascular function vs. chlorthalidone. * To test the hypothesis that, in women with prior pregnancy-induced hypertension, current chronic hypertension, and concentric LV remodeling, eplerenone improves early mitral diastolic inflow velocity/annular relaxation velocity vs. chlorthalidone. Participants will: * First receive pre-treatment with Amlodipine for 12 weeks prior to beginning the study medication (participants who are already receiving amlodipine monotherapy for at least 3 months prior to randomization will proceed directly to the baseline visit). * 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.

Interventions

Eplerenone 100 mg daily (Drug)
Participants with a history of pregnancy-induced hypertension 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 (Drug)
Participants with a history of pregnancy-induced hypertension 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 (Drug)
Participants taking eplerenone will also take a potassium placebo to self-administer daily over the 48-week duration of the study treatment.
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.

Eligibility criteria

Inclusion Criteria: * Female with a history of de novo preeclampsia, gestational hypertension, or preeclampsia superimposed on chronic hypertension (defined by ACOG criteria) in a singleton pregnancy. * At least one year from last pregnancy. * 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.

Conditions

Hypertension

Locations

Brigham and Women's Hospital — Boston, Massachusetts, United States
Massachusetts General Hospital — Boston, Massachusetts, United States

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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