A Phase 2 interventional study of spironolactone 25 mg orally once daily and Placebo tablet to match spironolactone in Preeclampsia and Gestational Hypertension, sponsored by Massachusetts General Hospital. Recruiting at 3 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-03.
Sponsored by Massachusetts General Hospital · Phase 2, Interventional, and Treatment
The hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) are associated with increased long-term maternal risk of developing cardiovascular disease. Recent evidence suggests that activation of the mineralocorticoid receptor promotes ongoing susceptibility to hypertension in women following hypertensive disorders of pregnancy. In addition, women with overweight/obesity are at increased risk for progression to chronic hypertension after experiencing hypertensive disorders of pregnancy. Among women with hypertensive disorders of pregnancy and pre-pregnancy overweight/obesity, the investigators will conduct a randomized trial to test the effect of pharmacologically blocking the mineralocorticoid receptor for three months after delivery on blood pressure and cardiac remodeling at nine months postpartum.
The hypertensive disorders of pregnancy (HDP, e.g., gestational hypertension and preeclampsia) are a leading cause of maternal and infant morbidity and mortality and are associated with increased long-term risk of maternal atherosclerotic cardiovascular disease (CVD) and heart failure. The American College of Cardiology and American Heart Association now recognize the HDP as a sex-specific CVD risk factor to guide prescription of preventive statin therapy. Beyond this focused recommendation, however, targeted strategies for CVD risk reduction in women with HDP are not yet established. Maternal overweight/obesity is a risk factor for accelerated progression from HDP to chronic hypertension, a key mediator of heightened long-term CVD risk in women with a history of HDP, and for adverse cardiac remodeling in pregnancy. Recent preclinical evidence suggests that the HDP induce heightened vascular smooth muscle cell mineralocorticoid receptor (MR) sensitivity that persists postpartum, promoting chronic hypertension and CVD. In addition, the recent POP-HT trial suggested that blood pressure control in the very early postpartum period has long-lasting effects on the risk of chronic hypertension and cardiac remodeling in women after HDP. Integrating these lines of evidence, the investigators hypothesize that short-term pharmacologic blockade of the MR in the early postpartum period after HDP will yield long-term maternal cardiovascular benefits in women with overweight/obesity. To test this hypothesis, the investigators will compare a strategy of adding low-dose spironolactone, a breastfeeding-compatible MR antagonist, or placebo to usual care for 3 months following delivery with HDP. This multi-site trial will randomize 204 women with HDP and pre-pregnancy overweight/obesity delivering at Massachusetts General Hospital, Brigham and Women's Hospital, and the University of Pittsburgh-Magee Womens Hospital. The investigators will test the effect of short-term adjunctive postpartum spironolactone on 24-hour ambulatory blood pressure (Aim 1) and postpartum cardiac remodeling by echocardiography (Aim 2) at 9 months postpartum (i.e., 6 months after completion of study treatment).
882 studies on the registry are indexed under Pre-Eclampsia; 237 are open to participants now.
This study's planned enrollment of 204 is above the median of 110 across 468 interventional studies indexed under Pre-Eclampsia.
Browse Pre-Eclampsia studies →Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.
Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants with Hypertensive disorders of pregnancy will receive placebo equivalent capsules to self-administer daily over the 12-week duration of the study treatment.
Drug: Placebo tablet to match spironolactone
Participants with hypertensive disorders of pregnancy will receive 25mg capsules of spironolactone to self-administer daily over the 12-week duration of the study treatment.
Drug: spironolactone 25 mg orally once daily
Participants with hypertensive disorders of pregnancy will receive 25mg capsules of spironolactone to self-administer daily over the 12-week duration of the study treatment.
Participants with Hypertensive disorders of pregnancy will receive placebo equivalent capsules to self-administer daily over the 12-week duration of the study treatment.
Mean 24-hour ambulatory diastolic blood pressure
24-hour BP monitoring will be performed as part of end-of-study assessments using a validated ambulatory BP monitor.
Time frame: 36 weeks
Left ventricular relative wall thickness (main echocardiographic outcome)
Relative wall thickness is calculated as 2\*posterior wall thickness/LV end-diastolic diameter as measured by transthoracic echocardiography.
Time frame: Baseline and 36 weeks
Mean 24-hour ambulatory systolic blood pressure
24-hour BP monitoring will be performed as part of end-of-study assessment using a validated ambulatory BP monitor. Mean 24-hour systolic BP will be calculated from the device data.
Time frame: 36 weeks
Mean diurnal ambulatory systolic blood pressure
24-hour BP monitoring will be performed as part of the end-of-study assessment using a validated ambulatory BP monitor. Mean diurnal systolic BP will be calculated from the device data.
Time frame: 36 weeks
Mean diurnal ambulatory diastolic blood pressure
24-hour BP monitoring will be performed as part of the end-of-study assessment using a validated ambulatory BP monitor. Mean diurnal ambulatory diastolic blood pressure will be calculated from the device data
Time frame: 36 weeks
Mean nocturnal ambulatory systolic blood pressure
24-hour BP monitoring will be performed as part of the end-of-study assessment using a validated ambulatory BP monitor. Mean nocturnal ambulatory systolic blood pressure will be calculated from the device data.
Time frame: 36 weeks
Mean nocturnal ambulatory diastolic blood pressure
24-hour BP monitoring will be performed as part of the post-treatment assessments using a validated ambulatory BP monitor. Mean nocturnal ambulatory diastolic blood pressure will be calculated from the device data.
Time frame: 36 weeks
Measured systolic blood pressure
At each visit, BP will be measured by study staff three times at one-minute intervals in accordance with multi-society guidelines for accurate measurement of blood pressure. The first measurement will be discarded, and the average of the second and third measurements will be recorded as the measured BP at each study visit.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Measured diastolic blood pressure
At each visit, BP will be measured by study staff three times at one-minute intervals in accordance with multi-society guidelines for accurate measurement of blood pressure. The first measurement will be discarded, and the average of the second and third measurements will be recorded as the measured BP at each study visit.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Readmission for hypertension
Postpartum readmission for hypertension will be captured.
Time frame: Through study completion (36 weeks post-randomization)
All-cause readmission
All postpartum readmission will be captured
Time frame: Through study completion (36 weeks post-randomization)
Daily defined doses of antihypertensive medication
Daily defined doses of antihypertensive medication will be quantified in accordance with the World Health Organization classification.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Time to discontinuation of all non-study drug antihypertensive medications
All medication changes made by treating clinicians will be captured.
Time frame: Through study completion (36 weeks post-randomization)
Escalation of antihypertensive regimen
All medication changes made by treating clinicians will be captured.
Time frame: Through study completion (36 weeks post-randomization)
Ratio of mitral E velocity to e' [E/e']
E/e', a measure of diastolic function, will be measured by transthoracic echocardiography.
Time frame: Baseline and 36 weeks
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: Baseline and 36 weeks
Peak tricuspid regurgitant jet velocity
Peak tricuspid regurgitant jet velocity, a measure of diastolic function, will be measured by transthoracic echocardiography using continuous wave Doppler
Time frame: Baseline and 36 weeks
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: Baseline and 36 weeks
Ratio of E to A [E/A]
E/A, a measure of diastolic function, will be measured by transthoracic echocardiography.
Time frame: Baseline and 36 weeks
Left ventricular mass index
Left ventricular mass will be calculated from transthoracic echocardiogarphy using the Devereux formula and indexed for body surface area
Time frame: Baseline and 36 weeks
Left ventricular ejection fraction
Left ventricular ejection fraction will be measured by transthoracic echocardiogarphy using the biplane method.
Time frame: Baseline and 36 weeks
Left atrial reservoir strain
Left atrial strain, a sensitive measure of end- diastolic pressure and atrial remodeling, will be quantified using TOMTEC.
Time frame: Baseline and 36 weeks
Peak global longitudinal strain
Left ventricular global longitudinal strain, a measure of subclinical cardiac dysfunction, will be quantified using TOMTEC.
Time frame: Baseline and 36 weeks
Interventricular septal wall thickness
Interventricular septal wall thickness will be measured by transthoracic echocardiography from the parasternal long axis view.
Time frame: Baseline and 36 weeks
Posterior wall thickness
Posterior wall thickness will be measured by transthoracic echocardiography from the parasternal long axis view.
Time frame: Baseline and 36 weeks
High-sensitivity cardiac troponin I
High-sensitivity cardiac troponin will be measured using standard clinical assays.
Time frame: Baseline, 12 weeks, and 36 weeks
N-terminal pro-B-type natriuretic peptide
NT-proBNP will be measured using standard clinical assays.
Time frame: Baseline, 12 weeks, and 36 weeks
Urine microalbumin/creatinine
Urine microalbumin/creatinine will be measured using standard clinical assays.
Time frame: 2 weeks, 12 weeks, and 36 weeks
Activin A
Activin A will be measured by ELISA.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Soluble fms-like tyrosine kinase receptor-1
sFlt-1 will be measured by ELISA.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Placental growth factor
Placental growth factor will be measured by ELISA.
Time frame: Baseline, 2 weeks, 12 weeks, and 36 weeks
Procollagen type I carboxyterminal propeptide
PICP will be measured by enzyme immunoassay.
Time frame: Baseline, 12 weeks, and 36 weeks
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