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

Sponsor
John O'Brien, MD (Other)
Overall Status
Recruiting
CT.gov ID
NCT03893630
Collaborator
(none)
250
1
3
55.2
4.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Acetylsalicylic Acid 81 mg
  • Drug: Acetylsalicylic Acid 162 mg
  • Other: Control
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia
Actual Study Start Date :
Apr 25, 2019
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Pulsatility Index (PI) [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.

    Secondary Outcome Measures

    1. Onset of Pre-eclampsia [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

    2. Severity of Pre-eclampsia [Throughout pregnancy and immediate postpartum ( 6 weeks after delivery)]

      Frequency women are identified with Severe Features of the disease

    3. 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)]

      Frequency of adverse neonatal outcomes

    4. Change in s-ICAM levels over time [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.

    5. Change in PIGF levels over time [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.

    6. Change in CRP levels over time [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.

    7. Change in IL-6 over time [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.

    8. Change in TNF over time [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Kentucky Lexington Kentucky United States 40536

    Sponsors and Collaborators

    • John O'Brien, MD

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    John O'Brien, MD, Professor, University of Kentucky
    ClinicalTrials.gov Identifier:
    NCT03893630
    Other Study ID Numbers:
    • 47841
    First Posted:
    Mar 28, 2019
    Last Update Posted:
    Jul 21, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by John O'Brien, MD, Professor, University of Kentucky
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 21, 2021