Clinical trial NCT04295850: Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)
Official title: Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Preeclampsia
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: March of Dimes
First posted: 2020-03-05
Enrollment: 130
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant patients at high risk for preeclampsia

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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Aim 1: PFA-100 closure time and risk of hypertensive disorder of pregnancy (HDP)
timeFrame: 8 months (delivery)
measure: Aim 2: Pharmacogenomics of aspirin
timeFrame: 2 weeks
measure: Aim 3: MicroRNAs and HDP
timeFrame: 8 months (delivery)
measure: Aim 4: Aspirin pharmacokinetics in pregnancy
timeFrame: 2 weeks
Secondary outcomes:
measure: Aim 1: Aspirin response
timeFrame: 2 weeks
measure: Aim 1: Prediction of HDP
timeFrame: 8 months (delivery)
measure: Aim 1: First trimester serum thromboxane and risk of HDP
timeFrame: 8 months (delivery)
measure: Aim 1: Third trimester serum thromboxane and risk of HDP
timeFrame: 8 months (delivery)
measure: Aim 2: Pharmacogenomics and Pregnancy outcome
timeFrame: 8 months (delivery)
measure: Aim 3: MicroRNA profile and aspirin therapy
timeFrame: 2 weeks
measure: Aim 4: Salicylic acid level and Serum Thromboxane
timeFrame: 2 weeks
measure: Predictors of preterm birth
timeFrame: 8 months (delivery)
measure: Predictors of preeclampsia
timeFrame: 8 months (delivery)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
References: