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

Preeclampsia Clinical Trial

— ASPIRIN  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06468202
• Other study ID #: Pro00079100
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 1, 2024
• Est. completion date: February 1, 2030

Study information

• Verified date: June 2024
• Source: Ohio State University
• Contact: Maged Costantine, MD, MBA
• Phone: 614-293-2222
• Email: Maged.Costantine[@]osumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10742
• Est. completion date: February 1, 2030
• Est. primary completion date: January 1, 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Live intrauterine gestation <16 6/7 weeks gestational age based on best obstetric estimate by the American College of Obstetricians and Gynecologists (ACOG) criteria,

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 elevated 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, lupus)

4. Or two or more moderate-risk criteria for HDP (per The U.S. Preventive Services Task Force (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 enrollment) iii) age =35 years (at time of expected estimated due date) iv) sociodemographic characteristics (Black race, government-assisted insurance) v) 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).

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),

2. Planned aspirin use in pregnancy for non-obstetrical indication (e.g., prior stroke/prior myocardial infraction),

3. Current aspirin use for obstetrical indications (e.g., related to IVF, or HDP) with inability to enroll and randomize in this trial before 13 0/7 weeks gestation (e.g., aspirin use started at 3 weeks gestation with continued use and approached for participation in this trial at 15 weeks' gestation), or more than 2 weeks of using aspirin if it was started >13 0/7 weeks (e.g., aspirin started for HDP prevention at 13 0/7 weeks but patient approached for participation at 15 2/7 weeks),

4. Age < 14 years,

5. Involuntarily confined or detained,

6. Considered as having a diminished decision-making capacity,

7. Obstetrical ultrasound suspicious for major congenital abnormality, known or suspected fetal aneuploidy, fetal demise, or planned pregnancy termination,

8. Participation in another trial that affects the primary outcome, without prior approval of the PI,

9. Plan to delivery outside participating site with inability to obtain medical records,

10. Monoamniotic twin gestation because of the risk of fetal demise and preterm delivery,

11. Participation in this trial in prior pregnancy,

12. Triplet or higher order pregnancy.

Related Conditions & MeSH terms

• Gestational Hypertension
• Hypertension
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia
• Preeclampsia
• Pregnancy Complications
• Toxemia

Intervention

Drug:
• Aspirin 81 mg
Participants will be assigned to 81mg Aspirin
• Aspirin 162 mg
Participants will be assigned to 162mg Aspirin

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine	Columbus	Ohio
United States	University of Texas, Houston	Houston	Texas
United States	University of Mississippi	Jackson	Mississippi
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Columbia University	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	University of Pittsburg Magee	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
Ohio State University	Northwestern University, Patient-Centered Outcomes Research Institute, Preeclampsia Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Preeclampsia	preeclampsia based on ACOG criteria	From >20 weeks gestation until hospital discharge following delivery, up to 22 weeks
Secondary	Preterm preeclampsia	Preeclampsia per ACOG criteria with delivery < 37 weeks'	From >20 weeks and = 36 weeks 6 days, up to 17 weeks
Secondary	Postpartum preeclampsia	Postpartum preeclampsia per ACOG criteria	From delivery weeks till 6 weeks postpartum; 6 weeks
Secondary	Gestational hypertension	Gestational hypertension per ACOG criteria	From >20 weeks until onset of labor, up to 22 weeks
Secondary	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
Secondary	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
Secondary	Bleeding complications (maternal)	Antepartum bleeding and Placental abruption	From randomization till delivery up to 36 weeks, up to 36 weeks
Secondary	Bleeding complications (maternal)	Postpartum hemorrhage	From delivery till hospital discharge, up to 1 week
Secondary	Adherence to aspirin	pill count	From randomization until last day of medication intake, up to 42 weeks
Secondary	Preterm birth	Delivery <37 weeks	At time of delivery
Secondary	Gestational age at birth	Gestational age in weeks at time of delivery	At time of delivery
Secondary	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
Secondary	Rate of SGA	Rate of birthweight <10th percentile	At time of birth
Secondary	Bleeding complications (neonatal)	Any neonatal intraventricular or intracranial hemorrhage	Up to 6 weeks post-delivery
Secondary	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