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

Purpose

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.

Condition

  • Pre-Eclampsia

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Genders
Female
Accepts Healthy Volunteers
Yes

Inclusion Criteria

(control)

• No risk factors for preeclampsia

Inclusion Criteria (pre-eclampsia)

- History of preterm preeclampsia

- Chronic hypertension

- Type 1 and Type 2 diabetes

- Renal diseases

- Autoimmune disease

Exclusion Criteria

  • Pregnant women younger than 18 years or older than 45 years
  • Multiple gestations
  • History of allergy (urticaria or anaphylaxis) to aspirin or aspirin-related products asthma that worsens after aspirin use
  • Patients with gastrointestinal or genitourinary bleeding
  • Patients with peptic ulcer disease
  • Patients with severe liver dysfunction
  • Patients who have undergone bypass surgery
  • Patients on anticoagulant medication(s)
  • Women with anomalous fetus

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Control Group
Patients will receive standard of care.
  • Other: Control
    Standard of Care
Experimental
Acetylsalicylic Acid 81mg
Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin).
  • Drug: Acetylsalicylic Acid 81 mg
    Patients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.
    Other names:
    • Aspirin
Experimental
Acetylsalicylic Acid 162mg
Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin).
  • Drug: Acetylsalicylic Acid 162 mg
    Patients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.
    Other names:
    • Aspirin

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536
Contact:
John M O'Brien, MD
859-218-0765
john.obrien2@uky.edu

More Details

NCT ID
NCT03893630
Status
Recruiting
Sponsor
John O'Brien, MD

Study Contact

Aarthi Srinivasan, MD, MS
8592180765
asr224@uky.edu

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.