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

John O'Brien, MD

Status and phase: Completed; Phase 2

Conditions: Pre-Eclampsia

Treatments: Drug: Acetylsalicylic Acid 162 mg; Other: Control; Drug: Acetylsalicylic Acid 81 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03893630

47841

Details and patient eligibility

About

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.

Full 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.

Enrollment: 208 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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208 participants in 3 patient groups

Control Group

Active Comparator group

Description:

Patients will receive standard of care.

Treatment:

Other: Control

Acetylsalicylic Acid 81mg

Experimental group

Description:

Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin).

Treatment:

Drug: Acetylsalicylic Acid 81 mg

Acetylsalicylic Acid 162mg

Experimental group

Description:

Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin).

Treatment:

Drug: Acetylsalicylic Acid 162 mg