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1/2 A randomized controlled trial of pravastatin to prevent preeclampsia in high-risk women

1/2 普伐他汀预防高危女性先兆子痫的随机对照试验

基本信息

批准号：
10705607
负责人：
Maged Costantine
金额：
--
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10705607
关键词：
3-hydroxy-3-methylglutaryl-coenzyme A 37 weeks gestation Address Adult Adverse event Angiogenesis Inhibitors Angiogenic Factor Animals Authorization documentation Basic Science Biological Birth Weight Budgets Cardiovascular Diseases Cardiovascular system Cessation of life Characteristics Clinical Trials Complication Data Coordinating Center Development Direct Costs Dose Double-Blind Method Drug Kinetics Effectiveness Endoglin Endothelium Evaluation Event Exposure to Fetal Death Fetal safety Fetus Funding Gestational Age Grant Growth Half-Life Hepatic High Risk Woman Human Hydroxymethylglutaryl-CoA Reductase Inhibitors Hypertension Inflammation Injury Letters Life Maternal-Fetal Medicine Units Network Maternal-fetal medicine Mission Morbidity - disease rate Mothers Multicenter Studies National Heart, Lung, and Blood Institute National Institute of Child Health and Human Development Neonatal Neonatal Mortality Obstetric Fetal Pharmacology Organ failure Oxidative Stress Oxidoreductase PGF gene Pathogenicity Pathway interactions Patients Pharmaceutical Preparations Phase Pilot Projects Placebos Postpartum Period Pravastatin Pre-Eclampsia Pregnancy Pregnancy Complications Pregnancy Outcome Pregnancy Rate Pregnant Women Premature Birth Prevention Primary Prevention Property Prophylactic treatment Randomized Randomized, Controlled Trials Recording of previous events Recurrence Renal clearance function Research Risk Risk Factors Risk Reduction Role Route Safety Secondary Prevention Seizures Seminal Series Serious Adverse Event Severities Teratogens Vascular Endothelial Growth Factor Receptor-1 Woman animal data cardiovascular disorder prevention cardiovascular disorder risk clinical center cohort design effective therapy endothelial dysfunction experience fetal high risk hydrophilicity hypertensive improved indexing inhibitor maternal morbidity maternal outcome mortality neonatal morbidity neonatal outcome neonate pilot trial preclinical study prevent randomized placebo controlled trial randomized placebo-controlled clinical trial randomized trial success

项目摘要

ABSTRACT Preeclampsia complicates approximately 3% to 5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. Women who have experienced preeclampsia in one pregnancy are at high risk for preeclampsia in subsequent pregnancies with the magnitude of the risk depending on the severity and gestational age at delivery in the index pregnancy. Preeclampsia shares pathogenic similarities with adult cardiovascular diseases as well as many risk factors. Endothelial dysfunction and inflammation are fundamental for the initiation and progression of both. Prevention of preeclampsia using various supplements and medications have had limited success. In contrast, there is strong evidence that 3-hydroxy-3- methylglutaryl-coenzyme A reductase inhibitors (statins) are beneficial in primary and secondary prevention of cardiovascular mortality and other cardiovascular events. Biological plausibility, animal data, and pilot clinical trials support a similar role for pravastatin, a hydrophilic statin with a favorable safety profile, in preventing preeclampsia prevention. In addition, the current evidence from animal studies and human pregnancy exposure cohorts do not support previous teratogenicity claims of pravastatin. Therefore, we propose a multicenter, double-blind, placebo-controlled randomized clinical trial to determine whether prophylactic treatment with pravastatin administered early in pregnancy reduces preeclampsia in high-risk women. A total of 1,760 pregnant women at high risk for preeclampsia (due to history of preeclampsia in a prior pregnancy that required delivery before 360/7 weeks) will be randomized between 100/7 and 166/7 weeks to pravastatin 10 mg or similar-appearing placebo, daily at bedtime until delivery. Women and their neonates will be followed throughout pregnancy and up to 6 weeks post partum to address the primary aim: evaluate whether treatment with pravastatin reduces the recurrence rate of preeclampsia; as well as the following secondary aims: (1) evaluate whether pravastatin improves maternal and neonatal outcomes; (2) assess the maternal and fetal/ neonatal safety profile of pravastatin during pregnancy; and (3) determine whether pravastatin administration in pregnancy reverses the angiogenic imbalance associated with preeclampsia by reducing the concentrations of the anti-angiogenic factors soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and increasing that of placental growth factor PlGF (angiogenic).

摘要