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

November 30, 2022 updated by: John O'Brien, MD

Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Aarthi Srinivasan, MD, MS
  • Phone Number: 8592180765
  • Email: asr224@uky.edu

Study Contact Backup

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Katherine Vignes, MD
        • Sub-Investigator:
          • Robin Shoemaker, PhD
        • Sub-Investigator:
          • Aarthi Srinivasan, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Pulsatility Index (PI)
Time Frame: Three times between 11 and 32 weeks of gestation.
Uterine artery doppler will be used to assess impedance to flow in the uterine artery three times: at 11-16 weeks gestation, 18-22 weeks gestation, and 28-32 weeks gestation.
Three times between 11 and 32 weeks of gestation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Onset of Pre-eclampsia
Time Frame: Throughout pregnancy and postpartum ( 6 weeks after delivery)
Frequency of Disease during pregnancy and postpartum as defined by American College of Obstetrics and Gynecology (ACOG) criteria
Throughout pregnancy and postpartum ( 6 weeks after delivery)
Severity of Pre-eclampsia
Time Frame: Throughout pregnancy and immediate postpartum ( 6 weeks after delivery)
Frequency women are identified with Severe Features of the disease
Throughout pregnancy and immediate postpartum ( 6 weeks after delivery)
Composite Neonatal outcomes including frequency of Intraventricular hemorrhage (IVH), Bronchopulmonary dysplasia (BPD), Respiratory distress syndrome (RDS), Necrotising enterocolitis(NEC)
Time Frame: Neonatal period ( first 28 days after birth)
Frequency of adverse neonatal outcomes
Neonatal period ( first 28 days after birth)
Change in s-ICAM levels over time
Time Frame: 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 soluble Intercellular Adhesion Molecule (s-ICAM) levels over time.
Three times between 11 and 32 weeks of gestation
Change in PIGF levels over time
Time Frame: 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 placental growth factor (PIGF) levels over time.
Three times between 11 and 32 weeks of gestation
Change in CRP levels over time
Time Frame: 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.
Three times between 11 and 32 weeks of gestation
Change in IL-6 over time
Time Frame: 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.
Three times between 11 and 32 weeks of gestation
Change in TNF over time
Time Frame: 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.
Three times between 11 and 32 weeks of gestation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

John O'Brien, MD

Investigators

  • Principal Investigator: John M O'Brien, MD, University of Kentucky
  • Study Chair: Katherine Vignes, MD, University of Kentucky

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 25, 2019

Primary Completion (ANTICIPATED)

December 1, 2023

Study Completion (ANTICIPATED)

December 1, 2023

Study Registration Dates

First Submitted

March 1, 2019

First Submitted That Met QC Criteria

March 26, 2019

First Posted (ACTUAL)

March 28, 2019

Study Record Updates

Last Update Posted (ACTUAL)

December 2, 2022

Last Update Submitted That Met QC Criteria

November 30, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 47841

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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