Pravastatin for the prevention of recurrent hypertensive disorders of pregnancy: study protocol for a randomized, open-label, parallel-group, three-arm trial

BACKGROUND: Hypertensive disorders of pregnancy lead to a critically ill maternal/fetal state due to maternal organ failure and fetal dysfunction related to placental abruption or impaired placental circulation. No treatment with established efficacy for hypertensive disorders of pregnancy is currently available, and delivery is the only definitive treatment. This article describes the study protocol for a trial that aims to evaluate whether early pravastatin treatment is effective in preventing hypertensive disorders of pregnancy. METHODS: A randomized, open-label, parallel-group, three-arm trial will be conducted with aspirin administered as the baseline treatment across all groups. Pregnant women with a history of hypertensive disorders of pregnancy who are at high risk of developing hypertensive disorders of pregnancy will be recruited from four recruitment sites in Japan. The three interventions of the study comprise oral pravastatin 5 mg once daily with oral bayaspirin 100 mg once daily, oral pravastatin 10 mg once daily with oral bayaspirin 100 mg once daily, and oral bayaspirin 100 mg once daily alone. The primary outcome measure is the incidence of hypertension during pregnancy. The secondary outcome measures include incidence rates of preeclampsia and gestational hypertension, maternal serum soluble fms-like tyrosine kinase-1/placental growth factor ratio, as well as soluble fms-like tyrosine kinase-1 and placental growth factor levels, whether the mother is proteinuric, placental weight, umbilical cord blood lipid profile, the incidence of hypertensive disorders of pregnancy-related complications (placental abruption, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia), week at diagnosis of hypertensive disorders of pregnancy, incidence of severe hypertensive disorders of pregnancy, and neonatal outcomes (birth weight, percentage of small for gestational age neonates, neonatal intensive care unit admission rate, and auditory brainstem response). DISCUSSION: The results of this study are expected to have wide-ranging implications given the effects of hypertensive disorders of pregnancy on long-term maternal and child health, as well as health economics. TRIAL REGISTRATION: Japan Registry of Clinical Trials (Trial ID: jRCTs031230067; registered May 11, 2023; https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031230067 ).