Randomised Controlled Trial with Pravastatin versus Placebo for Prevention of Pre-eclampsia

INTERVENTION: Trade Name: Pravastatina 20 mg Product Name: Pravastatin Pharmaceutical Form: Capsule INN or Proposed INN: Pravastatin Sodium Other descriptive name: Pravastatina 20mg Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Pre‐eclampsia ; MedDRA version: 19.0 Level: PT Classification code 10036485 Term: Pre‐eclampsia System Organ Class: 10036585 ‐ Pregnancy, puerperium and perinatal conditions Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] PRIMARY OUTCOME: Main Objective: To examine if the use of Pravastatin starting at 11­‐14 weeks' gestation in women at increased risk of developing pre­‐eclampsia (high blood pressure in pregnancy) reduces the incidence and severity of this complication. Primary end point(s): Incidence of preterm pre­eclampsia (< 37 weeks). Secondary Objective: To examine if the use of Pravastatin reduces the incidence of early delivery due to complications from high blood pressure, fetal growth restriction, stillbirth or neonatal complications, rate of neonatal intensive care unit admission, the incidence of placental abruption (separation) and spontaneous preterm delivery before 34 weeks and 37 weeks. Timepoint(s) of evaluation of this end point: Once delivered, data on pregnancy outcome, including labour onset, gestational age at delivery, mode of delivery, development of hypertension in pregnancy, neonatal birth weight and gender, and other obstetrics complications, will be collected from the hospital maternity records or their general medical practitioners. In addition, the obstetric records of women with pre‐­existing or pregnancy associated hypertension will be examined to determine if the condition is pre‐­eclampsia requiring delivery before 37 weeks' gestation. SECONDARY OUTCOME: Secondary end point(s): • Incidence of early‐PE (<34 weeks) and total PE (at any gestation); ; • Neonatal birthweight below the 3rd, 5th and 10th centile; ; • Stillbirth or neonatal death due to any cause; ; • Stillbirth or neonatal death ascribed to PE or fetal growth restriction ; ; • Stillbirth or neonatal death in association with maternal or neonatal bleeding; ; • Rate of neonatal intensive care unit admission; ; • Composite measure of neonatal mortality and morbidity; ; • Placental abruption (clinically or on placental examination); ; • Spontaneous preterm delivery <34 weeks and <37 weeks Timepoint(s) of evaluation of this end point: Once delivered, data on pregnancy outcome, including labour onset, gestational age at delivery, mode of delivery, development of hypertension in pregnancy, neonatal birth weight and gender, and other obstetrics complications, will be collected from the hospital maternity records or their general medical practitioners. In addition, the obstetric records of all women with pre­existing or pregnancy associated hypertension will be examined to determine if the condition is pre­eclampsia requiring delivery before 34 weeks' gestation.; ; Neonatal outcomes will be collected from Special Care Baby Unit. INCLUSION CRITERIA: • Age > 18 years; • Singleton pregnancies; • Live fetus at 11‐13 weeks of gestation; • High‐risk for preterm‐PE at 11‐13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (placental growth factor); • Be fluent in the local language (otherwise interpreters will be used); • Informed and written consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 2000 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0