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

NCT ID: NCT03893630

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-25
• Study Completion Date: 2022-09-28

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.

Conditions

Pre-Eclampsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control Group

Patients will receive standard of care.

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: OTHER

Standard of Care

Acetylsalicylic Acid 81mg

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

Group Type: EXPERIMENTAL

Acetylsalicylic Acid 81 mg

Intervention Type: DRUG

Patients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.

Acetylsalicylic Acid 162mg

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

Group Type: EXPERIMENTAL

Acetylsalicylic Acid 162 mg

Intervention Type: DRUG

Patients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Control

Standard of Care

Intervention Type: OTHER

Other Intervention Names

Aspirin; Aspirin

Eligibility Criteria

Inclusion Criteria

• No risk factors for preeclampsia

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

John O'Brien, MD

OTHER

Sponsor Role: lead

Responsible Party

John O'Brien, MD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John M O'Brien, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Katherine Vignes, MD

Role: STUDY_CHAIR

University of Kentucky

Locations

University of Kentucky

Lexington, Kentucky, United States

Countries

United States

References

Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.

Reference Type: BACKGROUND

PMID: 28657417 (View on PubMed)

Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007 May 26;369(9575):1791-1798. doi: 10.1016/S0140-6736(07)60712-0.

Reference Type: BACKGROUND

PMID: 17512048 (View on PubMed)

Roberge S, Bujold E, Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2018 Mar;218(3):287-293.e1. doi: 10.1016/j.ajog.2017.11.561. Epub 2017 Nov 11.

Reference Type: BACKGROUND

PMID: 29138036 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

47841

Identifier Type: -

Identifier Source: org_study_id