Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension

June 25, 2021 updated by: Eastern Virginia Medical School

Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension: A Pilot Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School
        • Contact:
        • Contact:
        • Principal Investigator:
          • Tetsuya Kawakita, MD
        • Sub-Investigator:
          • Juliana Martins, MD
        • Sub-Investigator:
          • Elena Sinkovskaya, MD
        • Sub-Investigator:
          • Alfred Abuhamad, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aspirin
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.
Drug: Aspirin 81mg
81mg aspirin daily beginning between 12 and 16 weeks of pregnancy and continuing until delivery.
No Intervention: No Aspirin
Participants in this arm will receive no aspirin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preterm Preeclampsia
Time Frame: Prior to 37 weeks
Preeclampsia developed before 37 weeks
Prior to 37 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preeclampsia
Time Frame: 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.
After 37 weeks
Gestational Hypertension
Time Frame: 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.
After 20 weeks gestation
HELLP Syndrome
Time Frame: After 20 weeks gestation
Hemolysis, elevated liver enzymes, and low platelet count syndrome
After 20 weeks gestation
Eclampsia
Time Frame: After 20 weeks gestation
New-onset tonic-clonic, focal, or multifocal seizure in the absence of other causative conditions
After 20 weeks gestation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eastern Virginia Medical School

Collaborators

AMAG Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Tetsuya Kawakita, MD, Eastern Virginia Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2021

Primary Completion (Anticipated)

May 31, 2023

Study Completion (Anticipated)

May 31, 2023

Study Registration Dates

First Submitted

May 26, 2021

First Submitted That Met QC Criteria

May 26, 2021

First Posted (Actual)

June 1, 2021

Study Record Updates

Last Update Posted (Actual)

June 28, 2021

Last Update Submitted That Met QC Criteria

June 25, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AS1H

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pre-Eclampsia

Clinical Trials on Aspirin 81mg

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mauritius

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe