A Phase 2 interventional study of Eplerenone 100 mg daily and Chlorthalidone 25 mg daily in Hypertension, sponsored by Massachusetts General Hospital. Recruiting at 2 sites in United States. Open to female participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by Massachusetts General Hospital · Phase 2, Interventional, and Treatment
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:
Participants will:
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.
6,114 studies on the registry are indexed under Hypertension; 912 are open to participants now.
This study's planned enrollment of 90 is close to the median of 100 across 4,575 interventional studies indexed under Hypertension.
Browse Hypertension studies →Massachusetts General Hospital is the lead sponsor of 2,586 studies on the registry; 447 are open to participants now.
Of its 222 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 20, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive eplerenone 100 mg daily plus potassium placebo for 48 weeks
Drug: Eplerenone 100 mg daily · Drug: Potassium Placebo
Participants will receive chlorthalidone 25 mg plus potassium 20 mEq daily for 48 weeks
Drug: Chlorthalidone 25 mg daily · Drug: Potassium Chloride
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.
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.
Participants taking eplerenone will also take a potassium placebo to self-administer daily over the 48-week duration of the study treatment.
Participants taking chlorthalidone will also take 20 mEq of potassium to self-administer daily over the 48-week duration of the study treatment.
Change in Myocardial Flow Reserve (MFR)
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Ratio of mitral E velocity to e' [E/e']
E/e', a measure of diastolic function, will be measured by transthoracic echocardiography.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Rest Myocardial Blood Flow (MBF)
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Stress Myocardial Blood Flow (MBF)
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Subendocardial-Specific Myocardial Flow Reserve (MFR)
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Relative wall thickness
Relative wall thickness is calculated as 2\*posterior wall thickness/LV end-diastolic diameter as measured by transthoracic echocardiography.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Early diastolic septal mitral annular velocity [septal e']
Septal e', a measure of diastolic function, will be measured by transthoracic echocardiography using tissue Doppler.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Peak tricuspid regurgitant velocity
Peak tricuspid regurgitant jet velocity, a measure of diastolic function, will be measured by transthoracic echocardiography using continuous wave Doppler.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial volume index
Left atrial volume index will be measured by transthoracic echocardiogarphy using the biplane method and indexed for body surface area.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Left atrial reservoir strain
Left atrial strain, a sensitive measure of end-diastolic pressure and atrial remodeling, will be quantified using TOMTEC.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Peak global longitudinal strain
Left ventricular global longitudinal strain, a measure of subclinical cardiac dysfunction, will be quantified using TOMTEC.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Renal blood flow
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Retinal vessel density
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of High-sensitivity cardiac troponin I
High-sensitivity cardiac troponin I, a marker of cardiovascular injury and remodeling, will be measured via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Level of N-terminal pro-B-type natriuretic peptide
NT-proBNP, a marker of cardiac wall stretch and remodeling, will be measured via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
High-sensitivity C-reactive protein
We will measure high-sensitivity C-reactive protein, a marker of inflammation and cardiovascular disease risk, via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Level of Interleukin-6
IL-6, a marker of inflammation and cardiovascular disease risk, will be measured via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of Transforming growth factor-beta1
TGF-B1, a marker of fibrosis, will be measured via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Concentration of procollagen type I carboxy-terminal propeptide
PICP, a marker of fibrosis, will be measured via blood collection.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Urine microalbumin-to-creatinine ratio
Microalbumin-to-creatinine will be measured through urine.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Score of Coronary artery calcium
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).
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
24-hour ambulatory blood pressure
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.
Time frame: Prior to randomization and after 48 weeks of randomized study treatment.
Plan to share: No
No publications or documents are linked to this record.
Started Mar 2026 (actual). Primary completion is estimated for Mar 2029, 35 months after the start.
Of 54 non-industry phase 2 interventional studies under Hypertension, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 75. This study's planned 35 months is below that.
Counting every sponsor, half of 110 studies reached it within 25 months; a quarter within 11 and three quarters within 56.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Eplerenone · Chlorthalidone · Potassium Chloride
Massachusetts General Hospital →