Prospects for the Prevention of Pregnancy-induced Hypertension and Preeclampsia Trial

Study Overview
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Brief Summary
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Hypertensive disorders of pregnancy (HDP) are with 50.000 deaths every year one of the major causes of maternal mortality worldwide, especially in low and middle income countries. This trial aims to determine whether a daily dose of combined low-dose aspirin, calcium, vitamin D3, folic acid and vitamin B12 in pregnancy reduces the incidence of pregnancy-induced hypertension in women at risk. Secondary and tertiary objectives include other maternal and neonatal outcomes.

Official Title
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Prospects for the Prevention of Pregnancy-induced Hypertension and Preeclampsia (4P) - a Randomised, Placebo-controlled, Double-blind Clinical Trial

Conditions
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Pregnancy Induced Hypertension

Intervention / Treatment
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* Drug: Combined aspirin and multinutrient supplement
* Other: Daily text reminder text messages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: <16 weeks of gestation and over 18 years of age, Intention to have subsequent antenatal visits and delivery at the same clinic. Can receive text messages by phone or through the phone of a proxy. A moderate to high risk (>20%) of developing PIH Exclusion Criteria: Pre-existing hypertension or hypertension before 20 weeks gestation. Likely non-compliance with the protocol in view of the treating physician Comorbidity interfering with the protocol Known contraindications to Investigational Product components

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined aspirin and multinutrient supplement<br>In a single capsule, the following will be combined: 80mg low-dose aspirin, 1.2 grams calcium, 600 IU vitamin D, 5mg folic acid and 1000 ug vitamin B12 | Drug: Combined aspirin and multinutrient supplement<br>* Single capsule with 80mg low-dose aspirin, 1.2 grams calcium, 600 IU vitamin D, 5mg folic acid and 1000 ug vitamin B12 mixed.<br>Other: Daily text reminder text messages<br> <br> |
| Placebo Comparator: Placebo<br>5mg folic acid, cellulose filler | Other: Daily text reminder text messages<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of pregnancy-induced hypertension (PIH) in pregnancy | Development of a de novo systolic blood pressure (SBP) of > 140 mmHg, diastolic blood pressure (DBP) of >90 mmHg, measured at least twice. | up to 2 days after delivery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal/obstetric outcomes | maternal death, preeclampsia, eclampsia, hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, hemorrhage, caesarian section, other complications during pregnancy or delivery | 6-16 weeks gestation, 16-24 weeks gestation, 26-36 weeks gestation, delivery and first days after | 
| Neonatal and infant outcomes | preterm birth, Intra uterine death, stillbirth, neonatal mortality, congenital abnormality, Neonatal Intensive Care Unit (NICU) admission or pediatrician referral, birth weight, small for gestational age, apgar scores, other adverse effects. Infant outcomes: weight and height, health, occurrence of disease and general health status | 6-16 weeks gestation, 16-24 weeks gestation, 26-36 weeks gestation, delivery and first days after | 
| Number of participants with (severe) adverse events as a measure of safety and tolerability | Number of patients with (severe) adverse events. Adverse events include any undesirable experience associated with the use of a medical product. Related to the product, bleeding incidences (including bruises), nausea, vomiting, will be explicitly reported. Severe adverse events are: death, life-threatening conditions, (prolonged) hospitalization, disability and permanent damage to mother or fetus, congenital abnormality, or other important (serious) medical events. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy induced hypertension, gestational hypertension, pre-eclampsia, preeclampsia, hypertensive disorders in pregnancy