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
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Maged Costantine其他文献
Maged Costantine的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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: