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:
- 金额:--
- 依托单位:
- 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:
- 关键词:3-hydroxy-3-methylglutaryl-coenzyme A37 weeks gestationAddressAdultAdverse eventAngiogenesis InhibitorsAngiogenic FactorAnimalsAuthorization documentationBasic ScienceBiologicalBirth WeightBudgetsCardiovascular DiseasesCardiovascular systemCessation of lifeCharacteristicsClinical TrialsComplicationData Coordinating CenterDevelopmentDirect CostsDoseDouble-Blind MethodDrug KineticsEffectivenessEndoglinEndotheliumEvaluationEventExposure toFetal DeathFetal safetyFetusFundingGestational AgeGrantGrowthHalf-LifeHepaticHigh Risk WomanHumanHydroxymethylglutaryl-CoA Reductase InhibitorsHypertensionInflammationInjuryLettersLifeMaternal-Fetal Medicine Units NetworkMaternal-fetal medicineMissionMorbidity - disease rateMothersMulticenter StudiesNational Heart, Lung, and Blood InstituteNational Institute of Child Health and Human DevelopmentNeonatalNeonatal MortalityObstetric Fetal PharmacologyOrgan failureOxidative StressOxidoreductasePGF genePathogenicityPathway interactionsPatientsPharmaceutical PreparationsPhasePilot ProjectsPlacebosPostpartum PeriodPravastatinPre-EclampsiaPregnancyPregnancy ComplicationsPregnancy OutcomePregnancy RatePregnant WomenPremature BirthPreventionPrimary PreventionPropertyProphylactic treatmentRandomizedRandomized, Controlled TrialsRecording of previous eventsRecurrenceRenal clearance functionResearchRiskRisk FactorsRisk ReductionRoleRouteSafetySecondary PreventionSeizuresSeminalSeriesSerious Adverse EventSeveritiesTeratogensVascular Endothelial Growth Factor Receptor-1Womananimal datacardiovascular disorder preventioncardiovascular disorder riskclinical centercohortdesigneffective therapyendothelial dysfunctionexperiencefetalhigh riskhydrophilicityhypertensiveimprovedindexinginhibitormaternal morbiditymaternal outcomemortalityneonatal morbidityneonatal outcomeneonatepilot trialpreclinical studypreventrandomized placebo controlled trialrandomized placebo-controlled clinical trialrandomized trialsuccess
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
先兆子痫合并约3%至5%的妊娠,仍然是母体和
新生儿发病率和死亡率。在一次妊娠中经历过先兆子痫的妇女处于高峰期
在后续妊娠中发生先兆子痫的风险,风险的大小取决于严重程度和
妊娠指标中分娩时的孕周。先兆子痫与成人的病原学相似
心血管疾病以及许多危险因素。内皮功能障碍和炎症
对两者的启动和发展都是至关重要的。应用多种补充剂预防子痫前期
而药物治疗的效果也有限。相反,有强有力的证据表明3-羟基-3-
甲基戊二酰辅酶A还原酶抑制剂(他汀类)在一级和二级预防中有益
心血管死亡率和其他心血管事件。生物学可信度、动物数据和临床试验
普伐他汀是一种亲水性他汀类药物,具有良好的安全性,试验支持普伐他汀在预防
预防子痫前期。此外,目前来自动物研究和人类怀孕的证据
暴露队列不支持普伐他汀先前的致畸声明。因此,我们提出一项
多中心、双盲、安慰剂对照的随机临床试验,以确定预防
孕期早期给予普伐他汀治疗可减少高危妇女的先兆子痫。总计
1,760名先兆子痫高危孕妇(由于先前怀孕时有先兆子痫病史
要求在360/7周前分娩)将在100/7周和166/7周之间随机给予普伐他汀10 mg或
外观相似的安慰剂,每天睡前服用,直到分娩。妇女和她们的新生儿将被跟踪
在整个怀孕期间和产后6周内解决主要目标:评估治疗
使用普伐他汀可降低先兆子痫的复发率;以及以下次要目标:
(1)评估普伐他汀是否改善了孕产妇和新生儿的结局;(2)评估了产妇和新生儿
妊娠期间普伐他汀对胎儿/新生儿的安全性;以及(3)确定普伐他汀是否
孕期给药通过减少先兆子痫相关的血管生成失衡
抗血管生成因子可溶性FMS样酪氨酸激酶-1(sFlt-1)和可溶性Enoglin的浓度
(Seng),增加胎盘生长因子PlGF(血管生成)的表达。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Maged Costantine其他文献
Maged Costantine的其他文献
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{{ truncateString('Maged Costantine', 18)}}的其他基金
Developing Extracellular Vesicle Based MPRINT Translational Resource Platform for Monitoring Therapeutics Response During Pregnancy
开发基于细胞外囊泡的 MPRINT 转化资源平台,用于监测妊娠期间的治疗反应
- 批准号:
10747545 - 财政年份:2023
- 资助金额:
-- - 项目类别:
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
- 批准号:
10087196 - 财政年份:2019
- 资助金额:
-- - 项目类别:
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
- 批准号:
10162643 - 财政年份:2019
- 资助金额:
-- - 项目类别:
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
- 批准号:
10455106 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Comprehensive evaluation of the safety and utility of pravastatin in prevention of preeclampsia in high-risk pregnant women
普伐他汀预防高危孕妇子痫前期的安全性和有效性综合评价
- 批准号:
9119186 - 财政年份:
- 资助金额:
-- - 项目类别: