Effectiveness of Two Aspirin Doses for Prevention of Hypertensive Disorders of Pregnancy: ASPIRIN TRIAL

NCT ID: NCT06468202

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

10742 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-18

Study Completion Date

2030-02-01

Brief Summary

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The overall goal of this large, pragmatic, comparative effectiveness trial is to test the hypothesis that among at-risk individuals, 162 mg/day aspirin is superior to 81 mg/day in preventing Hypertensive disorders of pregnancy (HDP), and that there are multiple factors associated with adherence with aspirin therapy that will be important to identify to enable optimal implementation of study findings and population-level benefits.

Detailed Description

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Hypertensive disorders of pregnancy (HDP), such as preeclampsia (PE) and gestational hypertension (gHTN), occur in \~15% of pregnant individuals, disproportionately affect self-identified non-Hispanic Black individuals (with the understanding that race is a socially defined construct and the inequity is related to social determinants of health), are increasing in frequency, and are associated with short- and long-term maternal and neonatal morbidities and mortality. There are currently no available therapeutics to treat individuals with HDP; thus, developing interventions for the prevention of HDP is of substantial public health significance. The U.S. Preventive Services Task Force (USPSTF) and other professional societies recommend or endorse the use of aspirin for prevention of HDP in individuals at high or moderate risk. However, there is great uncertainty regarding optimal dosing, whether there is heterogeneity of effectiveness of aspirin in reducing the risk of HDP among different populations, and what factors are associated with adherence.

The overall goal of this large, pragmatic, comparative effectiveness trial is to test the hypothesis that among at-risk individuals, 162 mg/day aspirin is superior to 81 mg/day in preventing HDP, and that there are multiple factors associated with adherence with aspirin therapy that will be important to identify to enable optimal implementation of study findings and population-level benefits. The trial will achieve the following specific aims:

Specific Aim 1: To compare the frequency of HDP (primary outcome), as well as other important secondary outcomes (gHTN, PE, preterm PE, PE-related adverse outcomes, aspirin-related safety outcomes, and patient-reported outcomes related to maternal health, pregnancy, and childbirth experiences) between the two aspirin treatment arms.

Specific Aim 2: To compare the gestational age at birth and the frequency of adverse perinatal outcomes (preterm birth, perinatal death, small-for-gestational-age birth, neonatal intensive care unit admission, and complications of prematurity), as well as patient-reported outcomes related to maternal-infant bonding between the two aspirin treatment arms.

Specific Aim 3: To use quantitative and qualitative analyses to elucidate facilitators and barriers associated with adherence to aspirin therapy in at-risk individuals during pregnancy in order to facilitate future implementation.

Conditions

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Hypertensive Disorders of Pregnancy Preeclampsia Gestational Hypertension

Keywords

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Hypertensive disorders of pregnancy Aspirin treatment Pregnancy Preeclampsia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A randomized double-blind, multicenter, comparative effectiveness trial
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Neither participants, providers, investigators or outcome assessors will know to which of these groups participants are assigned. In case of an emergency, however, the study doctor can get this information.

Study Groups

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81 mg Aspirin

Treatment A consisting of 81mg of aspirin (1 pill of 81mg \& 1 matching placebo) daily

Group Type EXPERIMENTAL

Aspirin 81 mg

Intervention Type DRUG

Participants will be assigned to 81mg Aspirin

162 mg Aspirin

Treatment B consisting of 162mg of aspirin (2 pills, each of 81mg) daily

Group Type EXPERIMENTAL

Aspirin 162 mg

Intervention Type DRUG

Participants will be assigned to 162mg Aspirin

Interventions

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Aspirin 81 mg

Participants will be assigned to 81mg Aspirin

Intervention Type DRUG

Aspirin 162 mg

Participants will be assigned to 162mg Aspirin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. live intrauterine gestation ≤16 6/7 weeks gestational age based on best clinical obstetric estimate,
2. age 14 years or older and able to provide informed consent,
3. at least one of the following high-risk criteria: i) any prior pregnancy complicated by preeclampsia ii) current pregnancy complicated by chronic hypertension diagnosed before randomization (ACOG) iii) pre-gestational diabetes (on medication for diabetes prior to pregnancy, or diabetes is diagnosed prior to randomization with hemoglobin A1C of 6.5% or greater or abnormal 3-hour glucose tolerance test) iv) twin gestation (including higher order pregnancy reduced to twins prior to 14 weeks) v) chronic kidney disease vi) autoimmune disease (e.g., antiphospholipid syndrome, systemic lupus erythematous)
4. or two or more moderate-risk criteria for HDP (per USPSTF), i) nulliparity (no prior delivery at or after 20 weeks 0 days of gestation) ii) obesity (body mass index ≥30 kg/m2 at time of randomization) iii) age ≥35 years (at time of expected estimated due date) iv) Black race v) low income vi) personal risk factors (previous pregnancy with low birth weight or SGA infant, previous adverse pregnancy outcome \[unexplained stillbirth\], placental abruption, interval \>10 years between pregnancies) vii) Family history of preeclampsia (i.e., mother or sister) viii) In vitro fertilization
5. patient not currently on aspirin OR patient on aspirin for obstetrical indications (e.g., related to IVF, or HDP) and: i- randomized before 130/7 weeks gestation, or ii- randomized on or after 13 0/7 weeks gestation and started aspirin within 2 weeks prior to randomization (e.g., aspirin started for HDP prevention at 12 0/7 weeks and patient randomized at 13 2/7 weeks).

Exclusion Criteria

1. known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., active peptic ulcer disease, nasal polyps, NSAID-induced asthma, active gastrointestinal bleeding, known G6PD deficiency, severe hepatic dysfunction, bleeding disorders, history of bariatric surgery),
2. current or planned aspirin use in pregnancy for non-obstetrical indication (e.g., prior stroke/prior myocardial infraction),
3. age \< 14 years,
4. involuntarily confined or detained,
5. considered as having a diminished decision-making capacity,
6. obstetrical ultrasound suspicious for major congenital abnormality, known or suspected fetal aneuploidy, fetal demise, or planned pregnancy termination,
7. participation in another trial that affects the primary outcome, without prior approval of the PI,
8. plan to deliver at an outside participating site with inability to obtain medical records,
9. monoamniotic twin gestation because of the risk of fetal demise and preterm delivery,
10. participation in this trial in prior pregnancy,
11. triplet or higher order pregnancy.
Minimum Eligible Age

14 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role collaborator

Preeclampsia Foundation

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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Maged Costantine

MD, MBA, Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maged Costantine, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Denise Sholtens, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Data Analysis and Coordinating Center

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status NOT_YET_RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

University of Mississippi

Jackson, Mississippi, United States

Site Status RECRUITING

University of New Mexico

Albuquerque, New Mexico, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

Columbus, Ohio, United States

Site Status RECRUITING

University of Pittsburg Magee

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Brown University

Providence, Rhode Island, United States

Site Status RECRUITING

University of Texas, Houston

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status NOT_YET_RECRUITING

Inova HealthSystem

Falls Church, Virginia, United States

Site Status RECRUITING

Eastern Virginia Medical School - Old Dominion University

Norfolk, Virginia, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Maged Costantine, MD, MBA

Role: CONTACT

Phone: 614-293-2222

Email: [email protected]

Kara Rood, MD

Role: CONTACT

Phone: 614-293-8045

Email: [email protected]

Facility Contacts

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Akila Subramaniam, MD, MPH

Role: primary

Donna Campbell, PhD

Role: backup

Kimberly Gregory, MD, MPH

Role: primary

Samia Saeb

Role: backup

Mary Norton, MD

Role: primary

Nuriye Sahin-Hodoglugil, DrPH

Role: backup

Michelle Kominiarek, MD

Role: primary

Catherine Arguelles

Role: backup

Rachel Morris, MD

Role: primary

Laura Coats

Role: backup

Christina Yarrington, MD

Role: primary

Karen S Taylor

Role: backup

Uma Reddy, MD

Role: primary

Cassandra Almonte

Role: backup

Kim Boggess, MD

Role: primary

Kelly Clark

Role: backup

Maged Costantine, MD, MBA

Role: primary

Kara Rood, MD

Role: backup

Hyagriv Simhan, MD

Role: primary

Jeanette Boyce

Role: backup

William Grobman, MD, MBA

Role: primary

Angelica Demartino

Role: backup

Baha Sibai, MD

Role: primary

Sunbola Ashimi, PhD

Role: backup

Torri Metz, MD

Role: primary

Amber Sowles, BSN, RN

Role: backup

Antonio Saad, MD

Role: primary

Michelle Cassidy, PhD, RN

Role: backup

George Saade, MD

Role: primary

Kristin Ayers

Role: backup

Anna Palatnik, MD

Role: primary

Alyssa Hernandez, DO

Role: backup

Other Identifiers

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Pro00079100

Identifier Type: -

Identifier Source: org_study_id