Low Doses of Aspirin in the Prevention of Preeclampsia (ASAPP)

November 10, 2023 updated by: Weill Medical College of Cornell University

A Randomized Controlled Trial Comparing Low Doses Of Aspirin In The Prevention Of Preeclampsia (ASAPP)

Preeclampsia (PE) is a morbid and potentially lethal complication of pregnancy and is more common in women with specific risk factors. Aspirin (ASA) is currently the only prophylactic therapy for preeclampsia in high-risk women to be recognized by the US Preventive Task Force and should be initiated early in the second trimester of pregnancy, before 16 weeks of gestation. However, currently there is no literature comparing various low-dose ASA formulations in the risk reduction of PE. In the United States, the currently available low-dose ASA is over the counter and is found in 81mg tablets. Therefore, when clinicians initiate therapy with low dose ASA, they may prescribe 1 or 2 tablets of 81mg aspirin per day depending on personal preference and cannot be assisted by evidence to guide their decision.This study aims to determine the incidence of preterm PE or PE with severe features in women taking either 81mg or 162mg in a randomized setting, from a single center. The investigators hypothesize that the information gained from this trial will permit a more accurate sample size calculation for a larger clinical trial powered to accept or reject our testing hypothesis. If our hypothesis is rejected and 162mg of daily ASA is not associated with a lower incidence of severe or preterm PE compared to 81mg, this may be due to lack of power to detect a smaller effect. The investigators would then evaluate the feasibility and results and determine whether a larger trial is reasonable.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Preeclampsia (PE) is a serious and potentially fatal complication of pregnancy. It is a placental disease characterized by an elevated blood pressure in the 3rd trimester with multisystem involvement (proteinuria, elevated liver enzymes, low platelet count and/or neurologic symptoms). PE can cause pulmonary edema, seizures, or stroke and is a leading cause of maternal mortality. The pregnancy outcomes are further worsened if PE develops before term. Women who have a history of PE in a prior pregnancy, diabetes, preexisting hypertension, kidney disease, multifetal gestation or autoimmune diseases are at an increased risk to develop PE in a subsequent pregnancy.

Clinical trials evaluating the benefits of low-dose aspirin (ASA) have used a wide range of doses from 60mg to 150mg orally daily with low-dose being defined as less than 325mg per day. Taking ASA (as opposed to placebo) is thought to reduce the risk of preeclampsia by 17%, without increasing the risk of major obstetric bleeding. The number needed to treat is only 19 women. ASA is currently the only prophylactic therapy for PE in high-risk women to be recognized by the US Preventive Task Force and should be initiated early in the second trimester of pregnancy, before 16 weeks of gestation.

There has also been more awareness that the efficacy of ASA in preventing preeclampsia is limited by the poor adherence of patients to this therapy. Indeed, a cross-sectional study has estimated that up to 46% of women (n=42) on ASA therapy may not be compliant to it, as determined by a validated Simplified Medication Adherence Questionnaire (SMAQ). Adherence is essential to the efficacy of ASA in preventing preterm preeclampsia. It would therefore be of interest to obtain more information about adherence to ASA in women who need this therapy.

Assessing molecular pathways in the development of PE may allow opportunity for earlier diagnosis, specific triaging of patients to closer monitoring and further development of preventative or curative treatment strategies. Samples will be biobanked for biomarker discovery in the future.

The current literature is lacking in evidence to recommend a specific daily dose of ASA. Recent meta-analyses have suggested that there may be a dose response in the protective effect of ASA for PE. As compared to 60mg per day, an ASA dose of 100mg per day was associated with a lower relative risk of PE (0.44 vs 0.57, p=0.36). A large study of 1776 women has compared a slightly higher dose of ASA (150mg per day) to placebo and found a decrease in preterm delivery (before 37 weeks) due to PE (OR 0.38, p=0.004). Meta-analyses have shown that any dose of ASA above 60mg per day is protective and should be used to prevent PE in high risk pregnancies.

To date, there has not been any studies comparing lower doses of ASA (such as 81mg, the traditional "baby aspirin" dose sold in the US) to higher "low-dose" ASA regimens (such as 162mg) in their ability to prevent preterm or severe PE in women who are at a high risk for this devastating disease.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • New York Presbyterian - Weill Cornell
      • New York, New York, United States, 11355
        • New York Presbyterian Queens

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

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Description

Patients are currently only being enrolled at the New York Presbyterian Weill Cornell Medicine and at the New York Presbyterian Queens campuses.

Inclusion Criteria:

Pregnant patients, ≥18 years old, at less than 16 weeks' gestation (as documented by ultrasound) with at least one of the following risk factors for developing PE:

  • PE in a prior pregnancy
  • Chronic hypertension (prior to pregnancy or before 20 weeks' gestation)
  • Type 1 or 2 diabetes
  • Renal disease (proteinuria ≥300mg/day or estimated GFR<90mL/min/1.73 m2)
  • Multifetal gestation
  • Autoimmune disease (e.g. systemic lupus erythematous, antiphospholipid syndrome)

Exclusion Criteria:

  • Patient with known intention to terminate pregnancy
  • Major fetal malformation seen on ultrasound
  • Contraindication to ASA therapy (including but not limited to allergy and high bleeding risk)

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 81mg ASA
Patients in Arm 1, will be instructed to take one tablet of 81mg aspirin per day.
Drug: acetylsalicylic acid
High risk pregnant women will be treated with daily aspirin during pregnancy.
Other Names:
  • ASA
  • aspirin
Active Comparator: 162mg ASA
Patients in Arm 2, will be instructed to take two tablets simultaneously orally once per day.
Drug: acetylsalicylic acid
High risk pregnant women will be treated with daily aspirin during pregnancy.
Other Names:
  • ASA
  • aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of preterm (<37 weeks) preeclampsia
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
The incidence of preterm (<37 weeks) preeclampsia in high risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.
9 months for each patient (from recruitment until 6 weeks postpartum)
Incidence of preeclampsia with severe features
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
The incidence of preeclampsia with severe features (American College of Obstetricians and Gynecologists [ACOG] 2019 definition) in high risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.
9 months for each patient (from recruitment until 6 weeks postpartum)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aspirin adherence
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
Evaluate and compare the adherence of pregnant women to 81mg and 162mg of daily low-dose aspirin using a validated, Simplified Medication Adherence Questionnaire (SMAQ).
9 months for each patient (from recruitment until 6 weeks postpartum)
Maternal and Fetal Outcomes
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
Compare maternal and fetal outcomes in pregnant women at a high risk for preeclampsia who are treated with either 81mg or 162mg of daily aspirin during pregnancy, including preeclampsia ≥37 weeks, severe maternal hypertension, preterm delivery, fetal growth restriction, placental abruption and maternal/fetal mortality.
9 months for each patient (from recruitment until 6 weeks postpartum)
Time-to-event for preeclampsia and gestational age at onset of PE
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
Compare the time-to-event for developing preeclampsia for women treated with 81mg vs 162mg of aspirin per day. The time to event analysis will be made using the gestational age at the onset of preeclampsia as a variable
9 months for each patient (from recruitment until 6 weeks postpartum)
Aspirin compliance
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
To assess the compliance to low dose aspirin in pregnant women that are at high risk for preeclampsia and compare compliance rates for women on 81mg vs 162mg of aspirin per day using urine studies for salicylates and serum analysis.
9 months for each patient (from recruitment until 6 weeks postpartum)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of co-morbidities on incidence of preeclampsia
Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum)
Assess the impact of specific co-morbidities (diabetes, chronic hypertension, renal disease and autoimmune disease), blood pressure control, age and race on the relationship between treatment group (81mg vs 162mg aspirin per day) and preeclampsia incidence.
9 months for each patient (from recruitment until 6 weeks postpartum)

Collaborators and Investigators

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

Sponsor

Weill Medical College of Cornell University

Investigators

  • Principal Investigator: Line Malha, MD, MS, Weill Medical College of Cornell University

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)

October 21, 2019

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

August 23, 2019

First Submitted That Met QC Criteria

August 23, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

November 14, 2023

Last Update Submitted That Met QC Criteria

November 10, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-05020160

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

No

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.

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