Effectiveness, Safety, and Cost-effectiveness of Salt Substitution in High-risk Pregnant Women for the Prevention of Hypertensive Disorders of Pregnancy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,200
- 试验地点
- 323
- 主要终点
- Change in Systolic Blood Pressure
研究概览
简要总结
The PREG-Salt study is to evaluate the effect, safety and cost-effectiveness of low-sodium salt in reducing blood pressure and preventing hypertensive disorders in pregnant women at high risk in China. The study will recruit about 3,200 participants from approximately 100 hospitals across multiple provinces in China. Eligible pregnant women (≤16 weeks of gestation) will be randomly assigned in a 1:1 ratio to the following 2 groups:
- Salt subsittute(intervention);
- Usual salt (control) .
The intervention will last until delivery. The study employs an adaptive two-phase design. An interim analysis after the first phase (n=400) will inform whether the trial continues into the second phase and if any adjustments to the sample size are needed. The primary outcomes are:
Phase 1: The mean systolic blood pressure across antenatal visits (excluding the last week before delivery).
Phase 2: New-onset hypertensive disorders of pregnancy and related adverse events from randomization to delivery.
详细描述
The PREG-Salt study is to evaluate the effect, safety and cost-effectiveness of low-sodium salt in reducing blood pressure and preventing hypertensive disorders in pregnant women at high risk in China. Specifically, the study aims include:
- to evaluate whether salt substitute significantly reduces mean blood pressure, while observing adherence and safety, in a high-risk population for hypertensive disorders of pregnancy.
- to further evaluate whether salt substitute significantly reduces the incidence of hypertensive disorders of pregnancy, while assessing its safety and cost-effectiveness.
The study is a two-phase, multicenter, randomized, double-blind, parallel-group controlled study. High-risk pregnant women at ≤16 weeks of gestation will be enrolled and randomly assigned in a 1:1 ratio to either the salt substitute(intervention) group or the usual salt (control) group. The study salt will be provided free of charge until delivery. Follow-up will be conducted through all antenatal visits and delivery to collect blood pressure data and information on the incidence of hypertensive disorders of pregnancy (including gestational hypertension, preeclampsia, eclampsia, death, stillbirth, preterm birth, etc.). The study employs an adaptive design. An interim analysis will be conducted after the completion of the first phase. Based on pre-specified efficacy and safety criteria, a decision will be made regarding the continuation of the study and potential adjustments to the subsequent sample size and randomization ratio.
The study will recruit about 3,200 participants(400 participants in the first phase) from approximately 100 hospitals (with an annual delivery volume of >1,000) at the county level or above, across multiple provinces in China.
Inclusion Criteria:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Singleton pregnancy with a viable fetus at ≤16 weeks of gestation.
- •Meets at least one of the following criteria (enrolled sequentially):
- •Systolic Blood Pressure (SBP) ≥130 mmHg and <160 mmHg at enrollment, OR current monotherapy with antihypertensive medications such as labetalol or nifedipine (priority enrollment).
- •At least one of the following 4 items: advanced maternal age (≥35 years), pre-pregnancy obesity (BMI ≥28 kg/m²), history of preeclampsia, or pre-existing type 1 or type 2 diabetes.
- •At least two of the following 5 items: history of adverse pregnancy outcome (e.g., fetal death, placental abruption, fetal growth restriction), personal history of gestational hypertension or family history of preeclampsia (mother or sister), history of gestational diabetes, obstructive sleep apnea, or pre-pregnancy overweight (BMI 24-28 kg/m²).
- •Routinely eats at least two meals per day at home (including meals brought from home).
- •Able to attend regular antenatal check-ups and is expected to complete the study follow-up.
- •Provides written informed consent. -
排除标准
- •SBP ≥160 mmHg or Diastolic Blood Pressure (DBP) ≥110 mmHg at enrollment.
- •Conditions or history associated with high uterine tension (e.g., polyhydramnios, macrosomia, hydatidiform mole); autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome).
- •History of chronic kidney disease, OR any antenatal check-up with a confirmed estimated Glomerular Filtration Rate (eGFR) <70 ml/min/1.73m², OR dipstick urine protein ≥2+.
- •Diagnosed hyperkalemia.
- •History of hypotension or syncope.
- •A household member who shares meals has a confirmed diagnosis of chronic kidney disease or hyperkalemia.
研究组 & 干预措施
Usual salt
Participants will continue to use usual salt (≥99% sodium chloride) in the preparation of home meals.
干预措施: Usual salt (Other)
Potassium-Enriched Salt substitutes
Participants will use a potassium-enriched salt substitute in place of usual salt for home-prepared meals. The study salt substitute consists of 25% potassium chloride and 75% sodium chloride.
干预措施: Potassium-enriched salt substitute (Other)
结局指标
主要结局
Change in Systolic Blood Pressure
时间窗: from baseline to 36-37 weeks of gestation
Mean change in systolic blood pressure across antenatal visits (excluding the week before delivery) during the follow-up period.
Change in Systolic Blood Pressure
时间窗: from baseline to 36-37 weeks of gestation
Mean change in systolic blood pressure across antenatal visits (excluding the week before delivery) during the follow-up period.
Incidence of new-onset hypertensive disorders of pregnancy and related maternal adverse events
时间窗: from randomization to delivery
A prespecified hierarchical composite endpoint including the first occurrence of any of the following events from randomization to delivery: 1）Maternal death or pregnancy loss; 2）New-onset preeclampsia, eclampsia, or placental abruption; 3）New-onset gestational hypertension or clinically meaningful elevation in blood pressure meeting diagnostic criteria.
次要结局
- Incremental Cost-Effectiveness Ratio (ICER)(from randomization to delivery)
- Gestational age at delivery(At delivery)
- Change in Diastolic Blood Pressure(from baseline to 36-37 weeks of gestation)
- The neonatal birth weight(At delivery)
- Mean change in Insomnia Severity Index (ISI) score(From baseline to 36-37 weeks of gestation)
- Mean change in spot urinary potassium(From baseline to 30-32 weeks of gestation)
- Change in Diastolic Blood Pressure(from baseline to 36-37 weeks of gestation)
- Incidence of maternal death(from randomization to delivery)
- Incidence of pregnancy loss(from randomization to delivery)
- The neonatal birth weight(At delivery)
- Incidence of new-onset hypertensive disorders of pregnancy(from randomization to delivery)
- Incidence of clinically meaningful increase in blood pressure(from randomization to delivery)
- Incidence of preeclampsia or eclampsia(from randomization to delivery)
- Incidence of all-cause maternal mortality(from randomization to delivery)
- Incidence of Placental abruption(from randomization to delivery)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(from randomization to delivery)
- Incidence of hyperkalemia(from randomization to delivery)
- Incidence of sudden cardiac death(from randomization to delivery)
- Incidence of hyponatremia(from randomization to delivery)
- Incidence of renal impairment(from randomization to delivery)
- Incidence of hypotension(from randomization to delivery)
- Incidence of preterm birth(At delivery)
- Incremental Cost-Effectiveness Ratio (ICER)(from randomization to delivery)
- Gestational age at delivery(At delivery)
- Incidence of neonatal adverse outcomes(delivery)
- Mean change in Insomnia Severity Index (ISI) score(From baseline to 36-37 weeks of gestation)
- Mean change in spot urinary potassium(From baseline to 30-32 weeks of gestation)