Clinical trial NCT06468202: Effectiveness of Two Aspirin Doses for Prevention of Hypertensive Disorders of Pregnancy: ASPIRIN TRIAL
Official title: Comparative Effectiveness of Two Aspirin Doses for Prevention of Hypertensive Disorders of Pregnancy: ASPIRIN TRIAL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypertensive Disorders of Pregnancy
Preeclampsia
Gestational Hypertension
Keywords: Hypertensive disorders of pregnancy
Aspirin treatment
Pregnancy
Preeclampsia
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Northwestern University
name: Preeclampsia Foundation
First posted: 2024-06-21
Enrollment: 10742
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized double-blind, multicenter, comparative effectiveness trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hypertensive Disorder of Pregnancy (HDP)
timeFrame: From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks
Secondary outcomes:
measure: Preeclampsia
timeFrame: From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks
measure: Preterm preeclampsia
timeFrame: From >20 weeks and ≤ 36 weeks 6 days, up to 17 weeks
measure: Postpartum preeclampsia
timeFrame: From delivery weeks till 6 weeks postpartum; 6 weeks
measure: Gestational hypertension
timeFrame: From >20 weeks until onset of labor, up to 22 weeks
measure: Severe maternal morbidity
timeFrame: From randomization up to 6 weeks postpartum, up to 48 weeks
measure: Core preeclampsia outcomes
timeFrame: From randomization up to 6 weeks postpartum, up to 48 weeks
measure: Bleeding complications (maternal)
timeFrame: From randomization till delivery up to 36 weeks, up to 36 weeks
measure: Bleeding complications (maternal)
timeFrame: From delivery till hospital discharge, up to 1 week
measure: Adherence to aspirin
timeFrame: From randomization until last day of medication intake, up to 42 weeks
measure: Preterm birth
timeFrame: At time of delivery
measure: Gestational age at birth
timeFrame: At time of delivery
measure: Core offspring/neonatal outcomes
timeFrame: up to 6 weeks post-delivery
measure: Rate of SGA
timeFrame: At time of birth
measure: Bleeding complications (neonatal)
timeFrame: Up to 6 weeks post-delivery
measure: Complications of prematurity and neonatal safety outcomes
timeFrame: Up to 6 weeks post-delivery
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
state: Ohio
city: Pittsburg
country: United States
facility: University of Pittsburg Magee
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Houston
country: United States
facility: University of Texas, Houston
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School - Old Dominion University
state: Virginia
Study officials:
affiliation: Ohio State University
name: Maged Costantine, MD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University Data Analysis and Coordinating Center
name: Denise Sholtens, PhD
role: PRINCIPAL_INVESTIGATOR
References: