Eplerenone vs Chlorthalidone for Chronic Hypertension
Cardiac Effects of Mineralocorticoid Receptor Antagonism After Preeclampsia
Recruiting
Phase 2Interventional Study
Hypertension
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 – 65
Sex
Female
Trial phase
Phase 2
Study type
Interventional
Purpose
Treatment
Participants needed
90 (estimated)
Sponsor
Massachusetts General Hospital · Other
Who this trial is looking for
This trial is looking for women who had preeclampsia during pregnancy and now have chronic high blood pressure. Participants will take daily capsules and attend several study visits over 48 weeks for monitoring and tests.
Are You a Good Fit for This Trial?
Must be takingAmlodipine
Rules you outHeart failureSevere valvular heart diseasePrimary aldosteronism
You may be able to join if
I am a woman with a history of preeclampsia in a singleton pregnancy.
I currently have chronic hypertension.
I have evidence of concentric left ventricular remodeling.
I am between 18 and 65 years old.
You may not be able to join if
I have used certain medications like MRAs or amiloride in the past 3 months.
I am currently pregnant or breastfeeding.
My blood pressure is too high despite treatment.
I have a BMI over 45 kg/m².
I have certain cardiovascular diseases.
I have diabetes.
My kidney function is too low.
I have a history of drug abuse.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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 rem…
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.
Trial Locations
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Eligibility Criteria
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 t…
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.
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