Treating early onset severe preeclampsia with pravastatin: an early phase clinical trial

Preeclampsia is pregnancy specific and complicates 5-8%. It is the leading cause of maternal and fetal morbidity and mortality. It is thought to occur as a result of abnormal attachment of the placenta to the uterine wall. This leads to a lack of oxygen and nutrient supply to the placenta. The ‘stressed’ and oxygen starved placenta releases ‘toxins’ that spread throughout the mother’s bloodsteam. They cause widespread injury of the mother’s blood vessels which then cause further damage to major organs: liver, kidneys and haematological impairment, nerves and the brain (causing seizures). Despite considerable research the only treatment available is termination of the pregnancy or delivery. In women that develop the disease early in pregnancy this exposes the fetus to considerable risk of the serious complications of preterm delivery. Pravastatin is a drug commonly taken by non-pregnant adults to lower the cholesterol in the blood. Importantly however, more recent research has found these drugs have also been shown to protect blood vessels. Therefore, it is possible they could mitigate the damage caused by the ‘toxins’ coming out of the placenta that injure the maternal blood vessels. If so, it could be potentially used as a treatment for severe preeclampsia. Just possibly, giving this drug to women with preterm preeclampsia might sufficiently quench the injury to the mother’s internal organs, allowing the pregnancy to safely continue to a gestation where the fetus is much less premature. Impressively, pravastatin has been tested in many animal models of preeclampsia and found to improve the disease. Importantly pravastatin didn’t cause harm in these animal models or when taken inadvertently in human case studies to either the mother or the fetus/neonate. We therefore propose a proof of concept early phase unblinded single arm study on the effect of pravastatin on the clinical course of early onset severe preeclampsia in humans. We will recruit 12 women and treat them with 40mg daily pravastatin. Inclusion criteria will be gestation 23+0 to 27+6 weeks, singleton pregnancy, with diagnosis of preeclampsia (increased blood pressure and high levels of protein in the urine).