Spironolactone to Improve Pregnancy-Associated Hypertension Trajectories
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 204
- 试验地点
- 4
- 主要终点
- Mean 24-hour ambulatory diastolic blood pressure
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females aged ≥18 years
- •HDP (gestational hypertension or preeclampsia) without pre-pregnancy chronic hypertension
- •BMI ≥25 kg/m2 prior to pregnancy or in the first trimester
- •Requirement for antihypertensive medication within one week of delivery
- •Ability to provide informed consent
排除标准
- •LV ejection fraction <50% or history of clinical heart failure with reduced or preserved ejection fraction
- •Hypertrophic or other genetic cardiomyopathy
- •Hyperkalemia: potassium >5.3 mEq/L
- •BMI at screening ≥50 kg/m2
- •Pre-pregnancy diabetes
- •Estimated glomerular filtration rate (eGFR) <60mL/min/1.73 m2
- •Cirrhosis
- •Primary aldosteronism
- •Intention to become pregnant within 9 months
- •Active substance abuse
- •Other serious medical illnesses or concerns about protocol adherence/ mortality within 9 months
- •Participation in another interventional clinical study
- •Hypersensitivity to spironolactone
- •Addison's disease
- •Concomitant use of eplerenone or finerenone
研究组 & 干预措施
Placebo: Control
Participants with Hypertensive disorders of pregnancy will receive placebo equivalent capsules to self-administer daily over the 12-week duration of the study treatment.
干预措施: Placebo tablet to match spironolactone (Drug)
Treatment: 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.
干预措施: spironolactone 25 mg orally once daily (Drug)
结局指标
主要结局
Mean 24-hour ambulatory diastolic blood pressure
时间窗: 36 weeks
24-hour BP monitoring will be performed as part of end-of-study assessments using a validated ambulatory BP monitor.
次要结局
- Left ventricular relative wall thickness (main echocardiographic outcome)(Baseline and 36 weeks)
- Mean 24-hour ambulatory systolic blood pressure(36 weeks)
- Mean diurnal ambulatory systolic blood pressure(36 weeks)
- Mean diurnal ambulatory diastolic blood pressure(36 weeks)
- Mean nocturnal ambulatory systolic blood pressure(36 weeks)
- Mean nocturnal ambulatory diastolic blood pressure(36 weeks)
- Measured systolic blood pressure(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Measured diastolic blood pressure(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Readmission for hypertension(Through study completion (36 weeks post-randomization))
- All-cause readmission(Through study completion (36 weeks post-randomization))
- Daily defined doses of antihypertensive medication(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Time to discontinuation of all non-study drug antihypertensive medications(Through study completion (36 weeks post-randomization))
- Escalation of antihypertensive regimen(Through study completion (36 weeks post-randomization))
- Ratio of mitral E velocity to e' [E/e'](Baseline and 36 weeks)
- Early diastolic septal mitral annular velocity [septal e'](Baseline and 36 weeks)
- Peak tricuspid regurgitant jet velocity(Baseline and 36 weeks)
- Left atrial volume index(Baseline and 36 weeks)
- Ratio of E to A [E/A](Baseline and 36 weeks)
- Left ventricular mass index(Baseline and 36 weeks)
- Left ventricular ejection fraction(Baseline and 36 weeks)
- Left atrial reservoir strain(Baseline and 36 weeks)
- Peak global longitudinal strain(Baseline and 36 weeks)
- Interventricular septal wall thickness(Baseline and 36 weeks)
- Posterior wall thickness(Baseline and 36 weeks)
- High-sensitivity cardiac troponin I(Baseline, 12 weeks, and 36 weeks)
- N-terminal pro-B-type natriuretic peptide(Baseline, 12 weeks, and 36 weeks)
- Urine microalbumin/creatinine(2 weeks, 12 weeks, and 36 weeks)
- Activin A(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Soluble fms-like tyrosine kinase receptor-1(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Placental growth factor(Baseline, 2 weeks, 12 weeks, and 36 weeks)
- Procollagen type I carboxyterminal propeptide(Baseline, 12 weeks, and 36 weeks)
研究者
Michael C. Honigberg
Principal Investigator
Massachusetts General Hospital