Clinical trial NCT03893630: Role of ASpirin in Placental and Maternal Endothelial Cell Regulation IN Pre-eclampsia
Official title: Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pre-Eclampsia
Keywords: aspirin
pulsatility index
doppler
uterine
acetylsalicylic acid
preeclampsia
blood pressure
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2019-03-28
Enrollment: 209
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Pulsatility Index (PI)
timeFrame: Three times between 11 and 32 weeks of gestation.
Secondary outcomes:
measure: Onset of Pre-eclampsia
timeFrame: Throughout pregnancy and postpartum ( 6 weeks after delivery)
measure: Severity of Pre-eclampsia
timeFrame: Throughout pregnancy and immediate postpartum ( 6 weeks after delivery)
measure: Composite Neonatal outcomes including frequency of Intraventricular hemorrhage (IVH), Bronchopulmonary dysplasia (BPD), Respiratory distress syndrome (RDS), Necrotising enterocolitis(NEC)
timeFrame: Neonatal period ( first 28 days after birth)
measure: Change in s-ICAM levels over time
timeFrame: Three times between 11 and 32 weeks of gestation
measure: Change in PIGF levels over time
timeFrame: Three times between 11 and 32 weeks of gestation
measure: Change in CRP levels over time
timeFrame: Three times between 11 and 32 weeks of gestation
measure: Change in IL-6 over time
timeFrame: Three times between 11 and 32 weeks of gestation
measure: Change in TNF over time
timeFrame: Three times between 11 and 32 weeks of gestation
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: John M O'Brien, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Katherine Vignes, MD
role: STUDY_CHAIR
References:
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.
citation: 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.
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.