Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)

Preeclampsia Clinical Trial

— APROACH  

Official title:

Antenatal Platelet Response On Aspirin and Correlation With HDP (Hypertensive Disorders of Pregnancy)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04295850
• Other study ID #: 19F.887
• Secondary ID: R21HD101127
• Status: Active, not recruiting
• Start date: August 21, 2020
• Est. completion date: July 30, 2023

Study information

• Verified date: August 2022
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: July 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 10 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Pre-Eclampsia
• Preeclampsia
• Toxemia

Intervention

Drug:
• Aspirin 81 mg
Aspirin 81mg daily PO

Locations

Country	Name	City	State
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Thomas Jefferson University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), March of Dimes

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aim 1: PFA-100 closure time and risk of hypertensive disorder of pregnancy (HDP)	Difference in first trimester PFA-100 closure time between patients started on aspirin who do and do not develop HDP	8 months (delivery)
Primary	Aim 2: Pharmacogenomics of aspirin	Difference in PFA-100 closure time with aspirin therapy based on platelet receptor genotype	2 weeks
Primary	Aim 3: MicroRNAs and HDP	Regression analysis to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels in first trimester are associated with risk of HDP	8 months (delivery)
Primary	Aim 4: Aspirin pharmacokinetics in pregnancy	Define population based pharmacokinetic model of aspirin in first trimester of pregnancy taking into consideration individual factors (gestational age, race, BMI, genotype)	2 weeks
Secondary	Aim 1: Aspirin response	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)	2 weeks
Secondary	Aim 1: Prediction of HDP	ROCC curve to determine threshold PFA-100 closure time after 1 week of aspirin therapy that is predictive of HDP	8 months (delivery)
Secondary	Aim 1: First trimester serum thromboxane and risk of HDP	Comparison between first trimester serum thromboxane in those with and without hypertensive disorder of pregnancy	8 months (delivery)
Secondary	Aim 1: Third trimester serum thromboxane and risk of HDP	Comparison between third trimester serum thromboxane in those with and without hypertensive disorder of pregnancy	8 months (delivery)
Secondary	Aim 2: Pharmacogenomics and Pregnancy outcome	Multiple regression analysis taking into consideration platelet receptor genotype, race, BMI, and other clinical characteristics and prediction of HDP	8 months (delivery)
Secondary	Aim 3: MicroRNA profile and aspirin therapy	Paired comparison to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels change before and after aspirin therapy	2 weeks
Secondary	Aim 4: Salicylic acid level and Serum Thromboxane	Association between serum salicylic acid with aspirin therapy and serum thromboxane with aspirin therapy	2 weeks
Secondary	Predictors of preterm birth	Multivariable logistic regression to evaluate markers predictive of preterm birth	8 months (delivery)
Secondary	Predictors of preeclampsia	Multivariable logistic regression to evaluate markers predictive of preeclampsia and preterm preeclampsia	8 months (delivery)