Role of ASpirin in Placental and Maternal Endothelial Cell Regulation IN Pre-eclampsia

Phase 2

Completed

Conditions: Pre-Eclampsia

Interventions: Other: Control
Drug: Acetylsalicylic Acid 81 mg
Drug: Acetylsalicylic Acid 162 mg

Registration Number: NCT03893630

Lead Sponsor: John O'Brien, MD

Brief Summary: Endothelial dysfunction and defective placental vascularization are hypothesized to be significant causes of preeclampsia. In preeclampsia, due to vascular endothelial dysfunction, vasoconstriction and platelet activation can result in severe features which alter pregnancy outcomes. However, studies have shown that acetylsalicylic acid (Aspirin) can decrease endothelial dysfunction leading to decreased platelet aggregation which reduces adverse outcomes. The objective of our study is to determine if Aspirin has a dose-dependent response for modifying biomarkers reflective of maternal endothelial dysfunction when indicated for preeclampsia prevention in a cohort of women identified at risk for developing preeclampsia.

Pregnant women who are at risk for preeclampsia will be randomized to receive either 81mg Aspirin or 162mg Aspirin daily starting from 11-16 weeks of gestation until 36 weeks of gestation. A third, control group of women at low risk for preeclampsia will not receive aspirin. All women will be assessed with uterine artery Doppler studies and mean arterial blood pressures at three time points during pregnancy. Blood, urine, and cord blood samples will also be collected.

Detailed Description: Eligible women will be identified in the late first or early second trimesters. Once recruited, women will be randomly assigned to either 81 mg or 162 mg per day dosing schedules. The randomization scheme will vary based on the body mass index (BMI) with separate schemes for women \<=30 kg/m2 versus \>30 kg/m2. Ultrasonographic assessment of biophysical biomarkers will be obtained at 11-16 weeks, 18-22 weeks, and 28-32 weeks gestation. Biologic samples of serum and urine will be obtained at the 11-16 week and 28-32 week visit. Upon delivery, cord blood and a placental specimen will also be obtained. Medication treatment will continue until 36 weeks gestation. Pregnancy and neonatal outcome data will be recorded.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 208

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Control	Patients will receive standard of care.
Acetylsalicylic Acid 81mg	Acetylsalicylic Acid 81 mg	Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin).
Acetylsalicylic Acid 162mg	Acetylsalicylic Acid 162 mg	Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin).

Primary Outcome Measures

Name	Time	Method
Change in Pulsatility Index (PI)	Three times between 11 and 32 weeks of gestation.	Uterine artery doppler is used to assess impedance to flow in the uterine artery three times: 11-16 weeks gestation(baseline), 18-22 weeks gestation (event 2), 28-32 weeks gestation (event 3). Data reported as change between 11-16 weeks gestation (baseline) and either 18-22 weeks gestation (event 2) or 28-32 weeks gestation (event 3). difference in uterine artery pulsatility index (PI) is calculated as the difference in PI for each patient between each trimester visit. PI at each visit will be calculated by averaging left-side and right-side PIs from each of three (or all available) images on each side for each patient using ultrasound technology. Unit of measure is a ratio: difference between the peak systolic and end-diastolic velocities divided by the mean flow velocity Relative change in uterine artery pulsatility index is a measure of flow to the uterus. A greater difference from the baseline value represents a greater improvement in placental perfusion.

Secondary Outcome Measures

Name	Time	Method
Onset of Pre-eclampsia	From enrollment at 11 weeks throughout pregnancy and postpartum ( 6 weeks after delivery), approximately 35 weeks	Frequency of Disease during pregnancy and postpartum as defined by American College of Obstetrics and Gynecology (ACOG) criteria
Severity of Pre-eclampsia	From enrollment at 11 weeks throughout pregnancy and immediate postpartum ( 6 weeks after delivery), approximately 35 weeks	Frequency women are identified with Severe Features of the disease
Composite Neonatal Outcomes Including Frequency of Intraventricular Hemorrhage (IVH), Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome (RDS), Necrotising Enterocolitis(NEC)	Neonatal period ( first 28 days after birth)	Frequency of adverse neonatal outcomes
Change in s-ICAM Levels Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first (baseline), second (event 2), and third (event 3) trimesters to measure changes in soluble Intercellular Adhesion Molecule (s-ICAM) levels over time.
Change in PIGF Levels Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first (baseline), second (event 2), and third (event 3) trimesters to measure changes in placental growth factor (PIGF) levels over time.
Change in CRP Levels Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in C-reactive protein (CRP) levels over time.
Change in IL-6 Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in interleukin 6 (IL-6) levels over time.
Change in TNF Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in tumor necrosis factor (TNFα) levels over time.
Gestational Age at Delivery	At Delivery, up to 41 weeks	measured in weeks, from the first day of the last menstrual cycle to delivery