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

Pre-Eclampsia Clinical Trial

— ASPERIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03893630
• Other study ID #: 47841
• Status: Recruiting
• Phase: Phase 2
• Start date: April 25, 2019
• Est. completion date: December 2023

Study information

• Verified date: November 2022
• Source: University of Kentucky
• Contact: Aarthi Srinivasan, MD, MS
• Phone: 8592180765
• Email: asr224[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

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.
• 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:
• Control
Standard of Care

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
John O'Brien, MD

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pulsatility Index (PI)	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	Onset of Pre-eclampsia	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)
Secondary	Severity of Pre-eclampsia	Frequency women are identified with Severe Features of the disease	Throughout pregnancy and immediate postpartum ( 6 weeks after delivery)
Secondary	Composite Neonatal outcomes including frequency of Intraventricular hemorrhage (IVH), Bronchopulmonary dysplasia (BPD), Respiratory distress syndrome (RDS), Necrotising enterocolitis(NEC)	Frequency of adverse neonatal outcomes	Neonatal period ( first 28 days after birth)
Secondary	Change in s-ICAM levels over time	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
Secondary	Change in PIGF levels over time	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
Secondary	Change in CRP levels over time	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
Secondary	Change in IL-6 over time	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
Secondary	Change in TNF over time	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in tumor necrosis factor (TNFa) levels over time.	Three times between 11 and 32 weeks of gestation