Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)
- Conditions
- Preeclampsia
- Interventions
- Registration Number
- NCT04295850
- Lead Sponsor
- Thomas Jefferson University
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 130
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Low Dose Aspirin Aspirin 81 mg 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.
- Primary Outcome Measures
Name Time Method Aim 2: Pharmacogenomics of aspirin 2 weeks Difference in PFA-100 closure time with aspirin therapy based on platelet receptor genotype
Aim 4: Aspirin pharmacokinetics in pregnancy 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 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) 8 months (delivery) Difference in first trimester PFA-100 closure time between patients started on aspirin who do and do not develop HDP
- Secondary Outcome Measures
Name Time Method Predictors of preeclampsia 8 months (delivery) Multivariable logistic regression to evaluate markers predictive of preeclampsia and preterm preeclampsia
Aim 1: First trimester serum thromboxane and risk of HDP 8 months (delivery) Comparison between first trimester serum thromboxane in those with and without hypertensive disorder of pregnancy
Aim 2: Pharmacogenomics and Pregnancy outcome 8 months (delivery) Multiple regression analysis taking into consideration platelet receptor genotype, race, BMI, and other clinical characteristics and prediction of HDP
Aim 1: Aspirin response 2 weeks Multiple logisitic regression analysis to evaluate factors (BMI, race, gestational age, genotype) associated with rate of nonresponse to aspirin therapy defined as (PFA-100\>150s)
Aim 3: MicroRNA profile and aspirin therapy 2 weeks Paired comparison to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels change before and after aspirin therapy
Aim 1: Prediction of HDP 8 months (delivery) ROCC curve to determine threshold PFA-100 closure time after 1 week of aspirin therapy that is predictive of HDP
Predictors of preterm birth 8 months (delivery) Multivariable logistic regression to evaluate markers predictive of preterm birth
Aim 1: Third trimester serum thromboxane and risk of HDP 8 months (delivery) Comparison between third trimester serum thromboxane in those with and without hypertensive disorder of pregnancy
Aim 4: Salicylic acid level and Serum Thromboxane 2 weeks Association between serum salicylic acid with aspirin therapy and serum thromboxane with aspirin therapy
Trial Locations
- Locations (1)
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States