Aspirin for High Blood Pressure During Pregnancy

(ASPIRIN Trial)

Recruiting at 13 trial locations

Overseen By Maged Costantine, MD, MBA

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Ohio State University

Must be taking: Aspirin

Disqualifiers: Aspirin allergy, Peptic ulcer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: From >20 weeks gestation until delivery, up to 22 weeks

10742 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether a higher dose of aspirin (162 mg) is more effective than a lower dose (81 mg) in preventing high blood pressure problems during pregnancy. Participants will take one of these doses to assess its effectiveness in preventing complications related to pregnancy-associated high blood pressure. Pregnant women who are 16 weeks or less and have risk factors such as a history of preeclampsia, current high blood pressure, or twins may be suitable for this study. The goal is to identify the most effective aspirin dose and understand factors influencing adherence to the treatment. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot participate if you are using aspirin for non-pregnancy-related reasons. If you are already on aspirin for pregnancy-related reasons, you may still be eligible under certain conditions.

What is the safety track record for these treatments?

Research has shown that taking a daily low-dose aspirin during pregnancy is generally safe. Studies have found it poses a low risk of causing serious issues for both the mother and the baby. For women at high risk of preeclampsia, a condition where blood pressure becomes too high during pregnancy, aspirin is the only recommended preventive measure. Experts suggest taking a low dose, such as 81 mg per day, after the first 12 weeks of pregnancy.

This trial tests two different doses: 81 mg and 162 mg. While 81 mg is commonly used and considered safe, the 162 mg dose is higher and has not been studied as extensively during pregnancy. Prospective participants should know that the standard low dose is safe, but the effects of the higher dose are still under investigation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using aspirin for high blood pressure during pregnancy because it's a low-cost, widely available option that could significantly impact maternal health. Unlike many treatments for high blood pressure in pregnancy, which often involve prescription medications with potential side effects, aspirin is a simple, over-the-counter solution. This trial is exploring two doses: 81 mg and 162 mg daily, which could lead to a tailored approach, optimizing safety and effectiveness. If successful, aspirin could offer a safer and more accessible way to manage high blood pressure in pregnant women, potentially reducing complications.

What evidence suggests that this trial's treatments could be effective for preventing hypertensive disorders of pregnancy?

Studies have shown that taking a low-dose aspirin, such as the 81 mg daily dose, can slightly reduce the risk of preeclampsia, a pregnancy complication that causes high blood pressure. Research indicates that aspirin can slightly lower blood pressure after two months of use. Evidence suggests that aspirin can reduce the risk of preeclampsia by about 17% without increasing the risk of serious bleeding. This trial compares two aspirin doses—81 mg and 162 mg—to determine which is more effective at preventing high blood pressure problems during pregnancy. Participants in this trial will receive either the 81 mg dose or the 162 mg dose, both considered low and generally safe for this purpose. ^{1 3 4 6 7}

Who Is on the Research Team?

Maged Costantine, MD

Principal Investigator

Ohio State University

Denise Sholtens, PhD

Principal Investigator

Northwestern University Data Analysis and Coordinating Center

Are You a Good Fit for This Trial?

This trial is for individuals at risk of developing hypertensive disorders during pregnancy, such as pre-eclampsia or high blood pressure. The study aims to find out if a higher dose of aspirin can prevent these conditions better than a lower dose.

Inclusion Criteria

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

I am 14 or older and can give my consent.

At least one of the following high-risk criteria: a) any prior pregnancy complicated by preeclampsia b) current pregnancy complicated by chronic hypertension diagnosed before randomization (ACOG) c) 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) d) twin gestation (including higher order pregnancy reduced to twins prior to 14 weeks) e) chronic kidney disease f) autoimmune disease (e.g., antiphospholipid syndrome, lupus) Or two or more moderate-risk criteria for HDP (per The U.S. Preventive Services Task Force (USPSTF)): a) nulliparity (no prior delivery at or after 20 weeks 0 days of gestation) b) obesity (body mass index ≥30 kg/m2 at time of enrollment) c) age ≥35 years (at time of expected estimated due date) d) sociodemographic characteristics (Black race, government-assisted insurance) e) 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

Plan to delivery outside participating site with inability to obtain medical records

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

Participation in this trial in prior pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 162 mg or 81 mg of aspirin daily to prevent hypertensive disorders of pregnancy

From >20 weeks gestation until delivery, up to 22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including postpartum outcomes

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin

Trial Overview The trial is testing two different doses of aspirin: one group will take 162 mg per day and another will take 81 mg per day. Researchers want to see which dosage is more effective in preventing high blood pressure-related complications in pregnancy.

How Is the Trial Designed?

Group I: 81 mg Aspirin Experimental Treatment 1 Intervention

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

Group II: 162 mg Aspirin Experimental Treatment 1 Intervention

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

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Preeclampsia Foundation

Collaborator

Trials

4

Recruited

50,900+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

In a study of 13 normotensive pregnant patients, low-dose aspirin (80 mg) significantly increased vascular sensitivity to angiotensin II, indicating a change in how blood vessels respond during pregnancy.

The findings suggest that low-dose aspirin may enhance the body's natural resistance to pregnancy-induced hypertension by altering the balance of certain compounds in the body, potentially improving outcomes for pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low-dose aspirin on angiotensin II pressor response in human pregnancy. Sanchez-Ramos, L., O'Sullivan, MJ., Garrido-Calderon, J.[2019]

Daily treatment with 50 mg of aspirin did not prevent the rise in maternal hypertension in high-risk pregnant women, but it improved fetal blood flow and reduced the need for neonatal intensive care, indicating a potential benefit for fetal health.

Aspirin significantly inhibited thromboxane A2 production while not affecting prostacyclin levels, suggesting it may help balance the body's blood vessel regulation towards a more protective state during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. Viinikka, L., Hartikainen-Sorri, AL., Lumme, R., et al.[2019]

Low-dose aspirin has been shown to be beneficial in preventing pre-eclampsia in high-risk pregnant women, based on results from four large clinical trials involving over 13,000 participants.

The use of low-dose aspirin is considered safe for mothers and their babies, although its effect on preventing fetal growth retardation is minimal and no significant therapeutic benefits were found.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin therapy in obstetrics. Wallenburg, HC.[2019]

Aspirin is considered safe for use during pregnancy at daily doses not exceeding 100mg and has been shown to effectively prevent pre-eclampsia and fetal growth restriction in high-risk patients.

However, aspirin has not demonstrated benefits for preventing vascular placental disease in low-risk patients or for unexplained recurrent miscarriages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. Belhomme, N., Doudnikoff, C., Polard, E., et al.[2018]

In a study of 46 pregnant women at risk for pregnancy-induced hypertension (PIH) or pre-eclampsia, low-dose aspirin (60 mg daily) significantly reduced the incidence of PIH compared to a placebo, with only 2 cases in the aspirin group versus 4 in the placebo group.

The treatment was found to be safe, with no adverse effects reported for either mothers or infants, suggesting that low-dose aspirin may help correct the imbalance of thromboxane A2 and prostacyclin, which is linked to these pregnancy complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. Wallenburg, HC., Dekker, GA., Makovitz, JW., et al.[2019]

Daily low-dose aspirin taken during pregnancy is effective in reducing the risk of preeclampsia, a serious condition that can affect both the mother and baby.

The use of low-dose aspirin is considered safe for pregnant individuals, making it a beneficial intervention to prevent adverse pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another good reason to recommend low-dose aspirin. Oyola, S., Kirley, K.[2018]

In a study of 65 pregnant women at high risk for pregnancy-induced hypertension, those treated with low-dose aspirin (100 mg daily) showed a significantly lower incidence of hypertension (11.8% vs. 35.5% in the placebo group) and pre-eclamptic toxemia (2.9% vs. 22.6%).

Aspirin treatment also corrected the imbalance between thromboxane A2 and prostacyclin metabolites, which may be a mechanism for its protective effect, with no serious side effects reported for mothers or newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. Schiff, E., Peleg, E., Goldenberg, M., et al.[2013]

A systematic review of studies indicates that low-dose aspirin (80-150 mg daily) taken in the first trimester (before 16 weeks) may effectively reduce the severity of preeclampsia in at-risk pregnancies.

In contrast, studies administering aspirin later in pregnancy showed mixed results, suggesting that the timing and dosage of aspirin are crucial for its effectiveness in preventing preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Role of Aspirin in Preeclampsia Prevention: State of the Art]. Campos, A.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12309040/

Effectiveness of low-dose aspirin in reducing the risk ... Evidence on the use of aspirin in women with chronic hypertension has indicated low effectiveness in preventing superimposed preeclampsia.

2. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/07/low-dose-aspirin-use-during-pregnancy

Low-Dose Aspirin Use During Pregnancy Based on the findings from the USPSTF and others, low-dose aspirin prophylaxis (81 mg/day) after 12 weeks of gestation modestly reduces the risk of preeclampsia ...

3. ahajournals.org ahajournals.org/doi/10.1161/01.HYP.30.3.589

Time-Dependent Effects of Low-Dose Aspirin ... When the pregnant women took ASA, BP continued to decrease slightly after the second month of treatment, without reaching the mean BP level obtained before ...

4. pcori.org pcori.org/research-results/2023/comparing-effectiveness-two-aspirin-doses-prevent-high-blood-pressure-complications-pregnancy

Comparing the Effectiveness of Two Aspirin Doses To ... This study compares the effectiveness of taking one or two pills of low-dose aspirin during pregnancy to prevent high blood pressure ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04070573

Low Doses of Aspirin in the Prevention of Preeclampsia Taking ASA (as opposed to placebo) is thought to reduce the risk of preeclampsia by 17%, without increasing the risk of major obstetric bleeding. The number ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK574452/

Aspirin Use to Prevent Preeclampsia and Related Morbidity ... Aspirin for women at high risk of preeclampsia is currently the only recommended method of prevention. Low dose aspirin is recommended by the World Health ...

7. uspreventiveservicestaskforce.org uspreventiveservicestaskforce.org/uspstf/recommendation/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

Aspirin Use to Prevent Preeclampsia and Related ... For pregnant persons: Prescribe low-dose (81 mg/d) aspirin after 12 weeks of gestation to persons who are at high risk for preeclampsia.