Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Aim 2: Pharmacogenomics of aspirin
研究概览
简要总结
This proposal has three aims to characterize the relationship between aspirin therapy, platelet function response, and prevention of hypertensive disorders of pregnancy (HDP) through a prospective, cohort study using pharmacokinetics, pharmacodynamics, pharmacogenomics and bioinformatics. The results of this proposal will provide necessary data for prospective study on individualized aspirin dose adjustment for prevention of HDP.
详细描述
This proposal has four aims to characterize the relationship between aspirin therapy, platelet function response, and prevention of HDP through a prospective, cohort study using pharmacodynamics, pharmacogenomics and bioinformatics. The results of this proposal will provide necessary data for prospective study on individualized aspirin dose adjustment for prevention of HDP.
Aim 1: Establish pharmacodynamic endpoints for aspirin in prevention of HDP Hypothesis: PFA-100 closure time and serum thromboxane/urinary dehydrothromboxane-B2 (dTX-B2) are pharmacodynamic markers of aspirin response and are predictive of HDP high risk pregnant patients.
Aim 2: Explore aspirin pharmacogenetics by assessing the relationship between platelet receptor genotype, aspirin response, and prevention of HDP Hypothesis: Platelet receptor genotype is associated with race and may result in reduced platelet response to aspirin therapy, and increased incidence of HDP.
Aim 3: Assess the utility of circulating microRNA as a marker of aspirin response in pregnancy and risk of HDP Hypothesis: Quantitative expression of selected miRNAs are biomarkers for response to aspirin therapy and risk of HDP.
Aim 4: Evaluate aspirin pharmacokinetics/pharmacodynamics Hypothesis: Individual factors influence aspirin pharmacokinetics/pharmacodynamics and may impact individual dosing of aspirin
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 10 Years 至 60 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant singleton, <16 weeks' gestation
- •At least one high risk factor for preeclampsia: prior preeclampsia, chronic hypertension, pregestational diabetes, chronic kidney disease, lupus, antiphospholipid antibody syndrome
排除标准
- •Contraindication to aspirin
- •Current or planned use of any other anticoagulation
- •Use of aspirin in pregnancy prior to enrollment
- •Known platelet disorder at time of enrollment
研究组 & 干预措施
Low Dose Aspirin
Pregnant singletons at high risk for preeclampsia based on:
- at least one high risk factor for preeclampsia: prior preeclampsia, chronic hypertension, pregestational diabetes, lupus, antiphospholipid antibody syndrome, or chronic kidney disease. OR
- at least two of the following: BMI>30, black race, state insurance, IVF pregnancy, advanced maternal age, nulliparous or >10yr from last delivery, prior adverse pregnancy outcome
who are planning to, but have not yet started, aspirin therapy <16 weeks' gestation. Patients will take 81mg aspirin as prescribed.
干预措施: Aspirin 81 mg (Drug)
结局指标
主要结局
Aim 2: Pharmacogenomics of aspirin
时间窗: 2 weeks
Difference in PFA-100 closure time with aspirin therapy based on platelet receptor genotype
Aim 4: Aspirin pharmacokinetics in pregnancy
时间窗: 2 weeks
Define population based pharmacokinetic model of aspirin in first trimester of pregnancy taking into consideration individual factors (gestational age, race, BMI, genotype)
Aim 3: MicroRNAs and HDP
时间窗: 8 months (delivery)
Regression analysis to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels in first trimester are associated with risk of HDP
Aim 1: PFA-100 closure time and risk of hypertensive disorder of pregnancy (HDP)
时间窗: 8 months (delivery)
Difference in first trimester PFA-100 closure time between patients started on aspirin who do and do not develop HDP
次要结局
- Aim 1: First trimester serum thromboxane and risk of HDP(8 months (delivery))
- Aim 2: Pharmacogenomics and Pregnancy outcome(8 months (delivery))
- Aim 1: Aspirin response(2 weeks)
- Aim 1: Prediction of HDP(8 months (delivery))
- Aim 3: MicroRNA profile and aspirin therapy(2 weeks)
- Predictors of preeclampsia(8 months (delivery))
- Predictors of preterm birth(8 months (delivery))
- Aim 1: Third trimester serum thromboxane and risk of HDP(8 months (delivery))
- Aim 4: Salicylic acid level and Serum Thromboxane(2 weeks)