Eplerenone versus chlorthalidone to improve heart blood vessel function after preeclampsia

Cardiac Effects of Mineralocorticoid Receptor Antagonism After Preeclampsia

This study will test whether eplerenone works better than chlorthalidone to improve coronary microvascular function in women who had preeclampsia and now have chronic high blood pressure and concentric left ventricular remodeling.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 65 Years
• Sex: Female
• Sponsor: Massachusetts General Hospital (Academic / other)
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT07238400 on ClinicalTrials.gov

What this trial studies

This randomized phase 2 trial enrolls women aged 18–65 with prior preeclampsia, current chronic hypertension, and evidence of concentric left ventricular remodeling. Participants receive 12 weeks of amlodipine pre-treatment and are then randomized to daily eplerenone (plus potassium placebo) or chlorthalidone (plus potassium) for the treatment period totaling 336 doses. Outcomes include changes in coronary microvascular function and cardiac structure and function measured by imaging and functional testing, with analyses to determine effects independent of blood pressure. The trial is conducted at Massachusetts General Hospital and Brigham and Women’s Hospital with NHLBI support.

Who should consider this trial

Good fit: Ideal candidates are women aged 18–65 who had preeclampsia in a singleton pregnancy, now have chronic hypertension and concentric LV remodeling, are not pregnant or breastfeeding, and meet the study's blood pressure and medication-use criteria.

Not a fit: Patients with diabetes, clinical atherosclerotic cardiovascular disease, reduced left ventricular ejection fraction (<40%), very high BMI (>45 kg/m²), recent mineralocorticoid antagonist use, uncontrolled hypertension above study thresholds, or who are pregnant/planning pregnancy are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, eplerenone could improve coronary microvascular function and promote healthier cardiac remodeling, lowering future cardiovascular risk for women after preeclampsia.

How similar studies have performed: Mineralocorticoid receptor antagonists have demonstrated benefits in heart failure and hypertension and preclinical data support MR involvement after preeclampsia, but randomized trials focused on coronary microvascular function after preeclampsia are novel.

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 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.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Michael Honigberg, MD — Massachusetts General Hospital
• Study coordinator: Samantha Murillo, MSc

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