Pregnancy Salt Substitution Trial for Hypertensive Disorders of Pregnancy Prevention (PREG-Salt)

Peking University

Status: Not yet enrolling

Conditions: Hypertensive Disorders of Pregnancy

Treatments: Other: Usual salt; Other: Potassium-enriched salt substitute

Study type: Interventional

Funder types: Other

Identifiers

NCT07294807

XMHEJH-WU

Details and patient eligibility

About

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:

1. Salt subsittute(intervention);
2. 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.

Full description

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:

1. 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.
2. 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:

1. Singleton pregnancy with a viable fetus at ≤16 weeks of gestation.

2. Meets at least one of the following criteria (enrolled sequentially):

   1. Systolic Blood Pressure (SBP) ≥130 mmHg and <160 mmHg at enrollment, OR current monotherapy with antihypertensive medications such as labetalol or nifedipine (priority enrollment).
   2. 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.
   3. 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).

3. Routinely eats at least two meals per day at home (including meals brought from home).

4. Able to attend regular antenatal check-ups and is expected to complete the study follow-up.

5. Provides written informed consent.

Exclusion Criteria:

1. SBP ≥160 mmHg or Diastolic Blood Pressure (DBP) ≥110 mmHg at enrollment.
2. Conditions or history associated with high uterine tension (e.g., polyhydramnios, macrosomia, hydatidiform mole); autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome).
3. 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+.
4. A confirmed diagnosis of hyperkalemia.
5. History of hypotension or syncope.
6. A household member who shares meals has a confirmed diagnosis of chronic kidney disease or hyperkalemia.

Outcome Measures:

Primary outcomes:

Phase 1: Mean change in systolic blood pressure. Phase 2: New-onset Hypertensive Disorders of Pregnancy and Related Maternal Adverse Events

Enrollment: 3,200 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Singleton pregnancy with a viable fetus at ≤16 weeks of gestation.

2. Meets at least one of the following criteria (enrolled sequentially):

   1. Systolic Blood Pressure (SBP) ≥130 mmHg and <160 mmHg at enrollment, OR current monotherapy with antihypertensive medications such as labetalol or nifedipine (priority enrollment).
   2. 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.
   3. 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).

3. Routinely eats at least two meals per day at home (including meals brought from home).

4. Able to attend regular antenatal check-ups and is expected to complete the study follow-up.

5. Provides written informed consent. -

Exclusion criteria

1. SBP ≥160 mmHg or Diastolic Blood Pressure (DBP) ≥110 mmHg at enrollment.
2. Conditions or history associated with high uterine tension (e.g., polyhydramnios, macrosomia, hydatidiform mole); autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome).
3. 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+.
4. Diagnosed hyperkalemia.
5. History of hypotension or syncope.
6. A household member who shares meals has a confirmed diagnosis of chronic kidney disease or hyperkalemia.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

3,200 participants in 2 patient groups, including a placebo group

Potassium-Enriched Salt substitutes

Experimental group

Description:

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.

Treatment:

Other: Potassium-enriched salt substitute

Usual salt

Placebo Comparator group

Description:

Participants will continue to use usual salt (≥99% sodium chloride) in the preparation of home meals.

Treatment:

Other: Usual salt