Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Change in Pulsatility Index (PI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Control Group
Patients will receive standard of care.
干预措施: Control (Other)
Acetylsalicylic Acid 81mg
Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin).
干预措施: Acetylsalicylic Acid 81 mg (Drug)
Acetylsalicylic Acid 162mg
Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin).
干预措施: Acetylsalicylic Acid 162 mg (Drug)
结局指标
主要结局
Change in Pulsatility Index (PI)
时间窗: Three times between 11 and 32 weeks of gestation.
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.
次要结局
- 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)
- Change in CRP Levels Over Time(Three times between 11 and 32 weeks of gestation)
- Change in IL-6 Over Time(Three times between 11 and 32 weeks of gestation)
- Change in TNF Over Time(Three times between 11 and 32 weeks of gestation)
- Gestational Age at Delivery(At Delivery, up to 41 weeks)
研究者
John O'Brien, MD
Professor
University of Kentucky