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

Phase 4

Recruiting

• Conditions: Preeclampsia; Hypertensive Disorders of Pregnancy; Gestational Hypertension
• Interventions: Drug: Aspirin 81 mg; Drug: Aspirin 162 mg

• Registration Number: NCT06468202
• Lead Sponsor: Ohio State University

Brief Summary

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

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 Timeline

• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-06-15
• Study First Posted: 2024-06-21
• Study Start: 2024-10-18
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-04
• Primary Completion: 2029-01-01
• Study Completion: 2030-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 10742

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
81 mg Aspirin	Aspirin 81 mg	Treatment A consisting of 81mg of aspirin (1 pill of 81mg \& 1 matching placebo) daily
162 mg Aspirin	Aspirin 162 mg	Treatment B consisting of 162mg of aspirin (2 pills, each of 81mg) daily

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Preterm preeclampsia	From >20 weeks and ≤ 36 weeks 6 days, up to 17 weeks	Preeclampsia per ACOG criteria with delivery \< 37 weeks'
Gestational hypertension	From >20 weeks until onset of labor, up to 22 weeks	Gestational hypertension per ACOG criteria
Severe maternal morbidity	From randomization up to 6 weeks postpartum, up to 48 weeks	Need for intensive care, maternal admission to a hospital within the first 42 days postpartum for obstetric complications, or blood product transfusion
Bleeding complications (neonatal)	Up to 6 weeks post-delivery	Any neonatal intraventricular or intracranial hemorrhage
Preeclampsia	From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks	preeclampsia based on ACOG criteria
Bleeding complications (maternal)	From delivery till hospital discharge, up to 1 week	Postpartum hemorrhage
Rate of SGA	At time of birth	Rate of birthweight \<10th percentile
Complications of prematurity and neonatal safety outcomes	Up to 6 weeks post-delivery	Composite of RDS, Grade III-IV IVH, PVL, Stage 2/3 NEC, BPD, Stage III or higher ROP, or early onset sepsis
Preterm birth	At time of delivery	Delivery \<37 weeks
Core preeclampsia outcomes	From randomization up to 6 weeks postpartum, up to 48 weeks	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)
Adherence to aspirin	From randomization until last day of medication intake, up to 42 weeks	pill count
Gestational age at birth	At time of delivery	Gestational age in weeks at time of delivery
Postpartum preeclampsia	From delivery weeks till 6 weeks postpartum; 6 weeks	Postpartum preeclampsia per ACOG criteria
Core offspring/neonatal outcomes	up to 6 weeks post-delivery	Composite and individual neonatal outcomes (Stillbirth, SGA, Neonatal mortality, Neonatal seizures, Admission to NICU, Respiratory support)

Trial Locations

Locations (12)

Eastern Virginia Medical School - Old Dominion University; 🇺🇸 Norfolk, Virginia, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Mississippi; 🇺🇸 Jackson, Mississippi, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

Columbia University; 🇺🇸 New York, New York, United States

University of North Carolina, Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine; 🇺🇸 Columbus, Ohio, United States

University of Pittsburg Magee; 🇺🇸 Pittsburg, Pennsylvania, United States

Brown University; 🇺🇸 Providence, Rhode Island, United States

University of Texas, Houston; 🇺🇸 Houston, Texas, United States