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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Gestational Hypertension; Hypertensive Disorders of Pregnancy
• Intervention / Treatment: Drug: Aspirin 81 mg; Drug: Aspirin 162 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 10742
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maged Costantine, MD, MBA; Phone Number: 614-293-2222; Email: Maged.Costantine@osumc.edu
• Study Contact Backup: Name: Kara Rood, MD; Phone Number: 614-293-8045; Email: Kara.Rood@osumc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Akila Subramaniam, MD, MPH; Email: asubramaniam@uabmc.edu
      • Contact: Donna Campbell, PhD; Phone Number: 205-996-6268; Email: dcampbell@uabmc.edu
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
      • Contact: Kimberly Gregory, MD, MPH
      • Contact: Samia Saeb; Email: Samia.Saeb@cshs.org
      • Principal Investigator: Kimberly Gregory, MD, MPH
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Mary Norton, MD
      • Contact: Nuriye Sahin-Hodoglugil, DrPH; Email: nuriye.sahin-hodoglugil@ucsf.edu
      • Contact: Mary Norton, MD; Phone Number: (415) 476-4080; Email: Mary.Norton@ucsf.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Sub-Investigator: Kiarri Kershaw, PhD, MPH
      • Contact: Michelle Kominiarek, MD; Email: Michelle.Kominiarek@nm.org
      • Contact: Catherine Arguelles; Email: catherine.marek@nm.org
      • Principal Investigator: Michelle Kominiarek, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • University of Mississippi
      • Principal Investigator: Rachel Morris, MD
      • Contact: Laura Coats; Email: Lcoats@umc.edu
      • Contact: Rachel Morris, MD; Email: morris@umc.edu
  • New Mexico
    • Albuquerque, New Mexico, United States, 27710
      • Recruiting
      • University of New Mexico
      • Contact: Christina Yarrington, MD; Email: CYarrington@salud.unm.edu
      • Contact: Karen S Taylor; Email: kataylor@salud.unm.edu
      • Principal Investigator: Christina Yarrington, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Principal Investigator: Matthew Hoffman, MD
      • Contact: Cassandra Almonte; Email: ca2344@cumc.columbia.edu
      • Contact: Matthew Hoffman, MD; Phone Number: (646) 284-5360; Email: mh4795@cumc.columbia.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina, Chapel Hill
      • Contact: Kim Boggess, MD; Email: kim_boggess@med.unc.edu
      • Principal Investigator: Kim Boggess, MD
      • Contact: Kelly Clark; Email: Kelly_Clark@med.unc.edu
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
      • Contact: Maged Costantine, MD, MBA; Phone Number: 614-293-2222; Email: Maged.Costantine@osumc.edu
      • Contact: Kara Rood, MD; Phone Number: 614-293-8045; Email: Kara.Rood@osumc.edu
      • Sub-Investigator: Kara Rood, MD
      • Sub-Investigator: Anne Trinh, MPH
      • Sub-Investigator: Ann McAlearney, ScD, MS
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburg Magee
      • Principal Investigator: Hyagriv Simhan, MD
      • Contact: Hyagriv Simhan, MD; Email: simhhn@upmc.edu
      • Contact: Jeanette Boyce; Email: tessje@upmc.edu
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Brown University
      • Contact: William Grobman, MD, MBA; Email: WGrobman@KentRI.org
      • Contact: Angelica Demartino; Phone Number: 48521 (401) 274-1122; Email: AMDemartino@CareNE.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas, Houston
      • Contact: Baha Sibai, MD; Email: Baha.M.Sibai@uth.tmc.edu
      • Contact: Sunbola Ashimi, PhD; Email: Sunbola.S.Ashimi@uth.tmc.edu
      • Principal Investigator: Baha Sibai, MD
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Torri Metz, MD; Email: Torri.Metz@hsc.utah.edu
      • Contact: Amber Sowles, BSN, RN; Phone Number: 801-585-5499; Email: Amber.Sowles@hsc.utah.edu
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Recruiting
      • Inova HealthSystem
      • Contact: Antonio Saad, MD; Email: Antonio.Saad@inova.org
      • Contact: Michelle Cassidy, PhD, RN; Phone Number: 703-776-4600; Email: Michelle.Cassidy@inova.org
    • Norfolk, Virginia, United States, 23501
      • Recruiting
      • Eastern Virginia Medical School - Old Dominion University
      • Principal Investigator: George Saade, MD
      • Contact: George Saade, MD; Email: SaadeGR@EVMS.edu
      • Contact: Kristin Ayers; Email: ayerskl@evms.edu
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Anna Palatnik, MD; Email: apalatnik@mcw.edu
      • Contact: Alyssa Hernandez, DO; Phone Number: 414-955-2781; Email: alyhernandez@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 81 mg Aspirin; Treatment A consisting of 81mg of aspirin (1 pill of 81mg & 1 matching placebo) daily	Drug: Aspirin 81 mg; Participants will be assigned to 81mg Aspirin
Experimental: 162 mg Aspirin; Treatment B consisting of 162mg of aspirin (2 pills, each of 81mg) daily	Drug: Aspirin 162 mg; Participants will be assigned to 162mg Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertensive Disorder of Pregnancy (HDP)	HDP defined as preeclampsia or antepartum gHTN based on ACOG criteria	From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preeclampsia	preeclampsia based on ACOG criteria	From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks
Preterm preeclampsia	Preeclampsia per ACOG criteria with delivery < 37 weeks'	From >20 weeks and ≤ 36 weeks 6 days, up to 17 weeks
Postpartum preeclampsia	Postpartum preeclampsia per ACOG criteria	From delivery weeks till 6 weeks postpartum; 6 weeks
Gestational hypertension	Gestational hypertension per ACOG criteria	From >20 weeks until onset of labor, up to 22 weeks
Severe maternal morbidity	Need for intensive care, maternal admission to a hospital within the first 42 days postpartum for obstetric complications, or blood product transfusion	From randomization up to 6 weeks postpartum, up to 48 weeks
Core preeclampsia outcomes	Composite and individual maternal outcomes (Mortality, Eclampsia, Stroke, Cortical blindness, Retinal detachment, Pulmonary edema, Acute kidney injury, Liver capsule hematoma, Placental abruption, Postpartum hemorrhage, Elevated liver enzymes, Thrombocytopenia, ICU admission, Mechanical ventilation)	From randomization up to 6 weeks postpartum, up to 48 weeks
Bleeding complications (maternal)	Antepartum bleeding and Placental abruption	From randomization till delivery up to 36 weeks, up to 36 weeks
Bleeding complications (maternal)	Postpartum hemorrhage	From delivery till hospital discharge, up to 1 week
Adherence to aspirin	pill count	From randomization until last day of medication intake, up to 42 weeks
Preterm birth	Delivery <37 weeks	At time of delivery
Gestational age at birth	Gestational age in weeks at time of delivery	At time of delivery
Core offspring/neonatal outcomes	Composite and individual neonatal outcomes (Stillbirth, SGA, Neonatal mortality, Neonatal seizures, Admission to NICU, Respiratory support)	up to 6 weeks post-delivery
Rate of SGA	Rate of birthweight <10th percentile	At time of birth
Bleeding complications (neonatal)	Any neonatal intraventricular or intracranial hemorrhage	Up to 6 weeks post-delivery
Complications of prematurity and neonatal safety outcomes	Composite of RDS, Grade III-IV IVH, PVL, Stage 2/3 NEC, BPD, Stage III or higher ROP, or early onset sepsis	Up to 6 weeks post-delivery

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Patient-Centered Outcomes Research Institute; Northwestern University; Preeclampsia Foundation
• Investigators: Principal Investigator: Maged Costantine, MD, MBA, Ohio State University; Principal Investigator: Denise Sholtens, PhD, Northwestern University Data Analysis and Coordinating Center

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 15, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Preeclampsia; Aspirin treatment; Hypertensive disorders of pregnancy
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Salicylates; Hydroxybenzoates; Aspirin
• Other Study ID Numbers: Pro00079100

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