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

Trial Summary

What is the purpose of this 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.

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 data supports the effectiveness of the drug aspirin for high blood pressure during pregnancy?

Research shows that taking low-dose aspirin during pregnancy can significantly reduce the risk of developing pregnancy-induced hypertension (high blood pressure) and preeclampsia, a serious condition that affects blood pressure and other organs. Studies found that aspirin helps balance certain chemicals in the body, reducing the risk of these complications. ^{1 2 3 4 5}

Is low-dose aspirin safe to use during pregnancy for high blood pressure?

Research shows that low-dose aspirin is generally safe for pregnant women and their babies when used to prevent high blood pressure and related conditions, with no serious side effects reported in studies. ^{2 3 5 6 7}

How does aspirin differ from other drugs for high blood pressure during pregnancy?

Aspirin is unique because it helps prevent high blood pressure during pregnancy by balancing certain chemicals in the body (thromboxane and prostacyclin) that affect blood flow, and it is considered safe at low doses. Unlike other treatments, it specifically targets the prevention of pre-eclampsia and related complications in high-risk pregnancies. ^{1 2 3 7 8}

Research Team

Maged Costantine, MD

Principal Investigator

Ohio State University

Denise Sholtens, PhD

Principal Investigator

Northwestern University Data Analysis and Coordinating Center

Eligibility Criteria

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

I do not have allergies to aspirin or conditions that make it unsafe for me to take it.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. [2019]

2. Portugal pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of low-dose aspirin on angiotensin II pressor response in human pregnancy. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Another good reason to recommend low-dose aspirin. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. [2019]

7. France pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Low-dose aspirin therapy in obstetrics. [2019]