Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
- Registration Number
- NCT04908982
- Lead Sponsor
- Eastern Virginia Medical School
- Brief Summary
In 2017, the American College of Cardiology and the American Heart Association changed the diagnostic criteria for hypertension in non-pregnant adults. The parameters for the diagnosis of stage 1 hypertension were revised from a systolic blood pressure (BP) of 140 to 130 mm Hg and a diastolic BP of 90 to 80 mm Hg. Based on new criteria, stage 1 hypertension is associated with a 2-3 fold increased risk of preeclampsia. There are no data regarding prevention of preeclampsia in women with stage 1 hypertension. Low-dose aspirin has been used during pregnancy to prevent preeclampsia for women at high-risk for preeclampsia. Although the precise mechanism remains uncertain, it is possible that low-dose aspirin improves placental perfusion, which results in a decreased rate of preeclampsia. A study that examines the effect of low-dose aspirin on placenta vasculature and tissue elastography by using novel ultrasound tools would be useful. The 2017 Aspirin for Evidence-Based Preeclampsia Prevention trial compared 150 mg aspirin with placebo in women at high-risk of preeclampsia based on a first-trimester screening. They found a significant decrease in the rate of preterm preeclampsia (4.3% vs. 1.6%; P \<0.01). Since this study used the screening algorithm including first-trimester serum markers and uterine artery Doppler, the generalizability in the U.S. women with stage 1 hypertension is limited. Our pilot study will examine 1) the effect of low-dose aspirin 81 mg in women with stage 1 hypertension on placental vasculature and shear-wave elastography; 2) the rate of preterm preeclampsia in women with stage 1 hypertension in a control group and in pregnancies treated with low-dose aspirin 81 mg; 3) feasibility of conducting a larger multicenter randomized controlled trial on this subject.
- Detailed Description
In 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) changed the diagnostic criteria for hypertension in non-pregnant adults.1 The parameters for the diagnosis of stage 1 hypertension were revised from a systolic blood pressure (BP) of 140 to 130 mm Hg and a diastolic BP of 90 to 80 mm Hg.2 Stage 1 hypertension based on the new criteria is associated with an increased risk of preeclampsia compared to normal BP (15-16% vs. 5-7%).3, 4 However, the American College of Obstetricians and Gynecologists (ACOG) continues to diagnose chronic hypertension in pregnancy as a systolic BP above 140 mm Hg and a diastolic BP of 90 mm Hg since there are no data regarding prevention of preeclampsia in women with stage 1 hypertension.5
Preeclampsia is a multi-organ, progressive disorder characterized by the new onset of hypertension with proteinuria or end-organ dysfunction.6 Preeclampsia is a major cause of morbidity such as eclampsia, pulmonary edema, myocardial infarction, stroke, coagulopathy, and renal failure and a leading cause of iatrogenic preterm birth and maternal mortality.7 Preeclampsia is also an economic burden to the health care system. The mean combined maternal and infant medical care costs for women with preeclampsia are significantly higher than those of uncomplicated women ($41,790 vs. $13,187 in 2015 dollars) with the main cost drivers being infant health care costs due to prematurity.8
It is hypothesized that preeclampsia is caused by an imbalance in prostacyclin and thromboxane A2 (TXA2) resulting in vascular disturbances and coagulation defects. Low-dose aspirin (60-150 mg/day) irreversibly acetylates cyclooxygenase (COX)-1, which results in decreased platelet synthesis of TXA2 without affecting vascular wall production of prostacyclin.9. 10 However, it is likely that preeclampsia is a result of poor placentation. In this pilot study, we will examine the effect of low-dose aspirin on placental perfusion by using novel ultrasound tools (Superb Micro-Vascular Imaging \[SMI\], Shear Wave Elastography \[SWE\], intensity analysis \[IA\], and Attenuation Imaging \[ATI\]). Superb Micro-Vascular Imaging (SMI) is a novel Doppler technique designed to improve the visualization of microscopic vessels, through a new adaptive algorithm, which dramatically enhances microvascular flow and removes artifacts. Shear Wave Elastography (SWE) is a new noninvasive ultrasound-based technology for the evaluation of soft tissue stiffness. Intensity Analysis (IA) is a technique that analyzes tissue homogeneity. Attenuation Imagining (ATI) measures beam attenuation by quantifying an attenuation coefficient (AC db/cm/MHz). Our group has developed longitudinal nomograms on placental vasculature to include uterine and spiral arteries on the maternal side and fetal placental arterioles and umbilical artery on the fetal side.11 Furthermore, longitudinal nomograms related to placental tissue structure, including shear wave elastography has been developed.12
Although the precise mechanism is uncertain, low-dose aspirin has been used during pregnancy to prevent or delay the onset of preeclampsia for women at high-risk for preeclampsia.13 The 2017 Aspirin for Evidence-Based Preeclampsia Prevention trial compared 150 mg aspirin with placebo in women at high-risk of preeclampsia based on a first-trimester screening.14 They found a significant decrease in the rate of preterm preeclampsia less than 37 weeks of gestation (4.3% vs. 1.6%; P \<0.01). Since this study used the screening algorithm including first-trimester serum markers and uterine artery Doppler, the generalizability of aspirin preeclampsia prevention in the U.S. women with stage 1 hypertension is limited.
Our long-term goal is to reduce preterm preeclampsia in women with stage 1 hypertension. We hypothesize that 1) spiral artery Pulsatility Index (PI) and Peak Systolic Velocity (PSV) and SWE is lower in women with stage 1 hypertension who receive low-dose aspirin 81 mg compared to those who do not receive low-dose aspirin; 2) Women with stage 1 hypertension who receive low-dose aspirin 81 mg have a lower rate of preterm preeclampsia compared to those who do not receive low-dose aspirin. To examine these hypotheses in a future, large randomized, controlled trial, our aims for this pilot study include the following:
Aim 1. To examine the change in placental vasculature and tissue elastography in women with stage 1 hypertension who receive low-dose aspirin 81 mg and those who do not receive low-dose aspirin.
Aim 2. To examine rates of preterm preeclampsia in women with stage 1 hypertension who receive low-dose aspirin 81 mg and those who do not receive low-dose aspirin.
Aim 3. To examine eligibility rate, recruitment rate, study compliance, and loss of follow-up rate. This information will be useful to assess feasibility of a future multicenter randomized controlled trial.
In summary, women with stage 1 hypertension are at an increased risk of preeclampsia. Low-dose aspirin may reduce the rate of preterm preeclampsia in women with stage 1 hypertension. In this pilot study, we will conduct an open label randomized controlled trial and obtain necessary information for a future multicenter randomized controlled trial.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 60
- Pregnant women from 6 0/7 to 13 6/7 weeks gestation
- 18-50 years old
- Systolic blood pressure of 130-139 mmHg or Diastolic blood pressure of 80-89 mmHg
- History of preeclampsia
- Multifetal gestation
- Chronic hypertension
- Pre-gestational diabetes
- Renal disease
- Autoimmune disease
- Aspirin allergy or hypersensitivity
- Presence of nasal polyps
- History of aspirin-induced bronchospasm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aspirin Aspirin 81mg Participants in this arm will be instructed to take 1 81mg aspirin daily beginning between weeks 12 and 16 of pregnancy and continuing until delivery.
- Primary Outcome Measures
Name Time Method Preterm Preeclampsia Prior to 37 weeks Preeclampsia developed before 37 weeks
- Secondary Outcome Measures
Name Time Method HELLP Syndrome After 20 weeks gestation Hemolysis, elevated liver enzymes, and low platelet count syndrome
Preeclampsia After 37 weeks Systolic blood pressure of 140 mmHg or more or diastolic blood pressure of 90 mmHg or more on two occasions at least four hours apart or a systolic blood pressure of 160 mmHg or more or diastolic blood pressure of 110 mmHg or more; and Proteinuria of 300mg or more per 24-hour urine collection or protein/creatinine ratio of 0.3 or more; or in the absence of proteinuria, new-onset hypertension with the new onset of any of the following severe features: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, new-onset headache unresponsive to medication.
Gestational Hypertension After 20 weeks gestation Systolic blood pressure of 140 mmHg or more or diastolic blood pressure of 90 mmHg or more on two occasions at least four hours apart with no proteinuria or severe features.
Eclampsia After 20 weeks gestation New-onset tonic-clonic, focal, or multifocal seizure in the absence of other causative conditions
Trial Locations
- Locations (1)
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School
🇺🇸Norfolk, Virginia, United States