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

NCT03893630 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 47841
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

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.

Conditions

Pre-Eclampsia

Keywords

aspirin; pulsatility index; doppler; uterine; acetylsalicylic acid; preeclampsia; blood pressure

Outcome Measures

Primary Outcomes (1)

• Change in Pulsatility Index (PI)

  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.

  Three times between 11 and 32 weeks of gestation.

Secondary Outcomes (9)

• Onset of Pre-eclampsia

  From enrollment at 11 weeks throughout pregnancy and postpartum ( 6 weeks after delivery), approximately 35 weeks

• Severity of Pre-eclampsia

  From enrollment at 11 weeks throughout pregnancy and immediate postpartum ( 6 weeks after delivery), approximately 35 weeks

• 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)

• Change in s-ICAM Levels Over Time

  Three times between 11 and 32 weeks of gestation

• Change in PIGF Levels Over Time

  Three times between 11 and 32 weeks of gestation

Study Arms (3)

Control Group

ACTIVE COMPARATOR

Patients will receive standard of care.

Other: Control

Acetylsalicylic Acid 81mg

EXPERIMENTAL

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

Drug: Acetylsalicylic Acid 81 mg

Acetylsalicylic Acid 162mg

EXPERIMENTAL

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

Drug: Acetylsalicylic Acid 162 mg

Interventions

Acetylsalicylic Acid 81 mg DRUG

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

Also known as: Aspirin

Acetylsalicylic Acid 81mg

Acetylsalicylic Acid 162 mg DRUG

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

Also known as: Aspirin

Acetylsalicylic Acid 162mg

Control OTHER

Standard of Care

Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No risk factors for preeclampsia
• History of preterm preeclampsia
• Chronic hypertension
• Type 1 and Type 2 diabetes
• Renal diseases
• Autoimmune disease

You may not qualify if:

• 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

Sponsors & Collaborators

• John O'Brien, MD: lead

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (3)

• 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.

  PMID: 28657417 BACKGROUND

• 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.

  PMID: 17512048 BACKGROUND

• 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.

  PMID: 29138036 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. John M. O'Brien
• Organization: University of Kentucky

john.obrien2@uky.edu

8592575158

Study Officials

• John M O'Brien, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Katherine Vignes, MD

  University of Kentucky

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 28, 2019
• Study Start: April 25, 2019
• Primary Completion: July 26, 2022
• Study Completion: September 28, 2022
• Last Updated: August 29, 2025
• Results First Posted: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)