Aspirin for Preeclampsia

Overseen By Colleen Duncan, RN

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Chicago

Must not be taking: Nonsteroidal anti-inflammatories

Disqualifiers: Cardiomyopathy, Hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether aspirin can improve heart function in women with preeclampsia, a pregnancy condition marked by high blood pressure and organ damage. Researchers aim to determine if taking aspirin after delivery can lower levels of Activin A, a protein linked to the condition. Participants will receive either aspirin, a placebo (a sugar pill), or no treatment, and researchers will monitor their progress. Women who are pregnant, diagnosed with preeclampsia, and expecting a single baby may be eligible to join. As a Phase 4 trial, this research examines how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you do not take any nonsteroidal anti-inflammatory drugs (like ibuprofen) while participating. If you are currently taking these, you will need to stop.

What is the safety track record for aspirin?

Research shows that low-dose aspirin is generally safe for pregnant individuals. Studies have found it does not significantly increase the risk of major bleeding during pregnancy. In fact, it can lower the chance of developing preeclampsia, a serious condition affecting blood pressure during pregnancy.

Previous studies have examined different doses of aspirin, such as 81 mg and 150 mg, and found them well-tolerated by most pregnant individuals. These studies reported no major safety concerns, suggesting aspirin is a safe option for those at risk of preeclampsia.

The FDA has approved aspirin for preventing preeclampsia in some pregnant individuals, supporting its safety for this use. It is important to consult a healthcare provider to understand personal risks and benefits before starting any treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for preeclampsia focus on managing symptoms and preventing complications, often involving medications like antihypertensives and magnesium sulfate. But aspirin is gaining attention for its potential to prevent the onset of severe symptoms. Unlike traditional treatments that primarily manage blood pressure, aspirin works by inhibiting platelet aggregation, which may help improve blood flow to the placenta. Researchers are excited because this approach could address a root cause of preeclampsia rather than just alleviating symptoms, potentially offering a simpler and more proactive solution for at-risk pregnancies.

What evidence suggests that aspirin might be an effective treatment for preeclampsia?

Research has shown that aspirin can lower the risk of preeclampsia, a condition affecting pregnant women. Studies have found that taking low-dose aspirin reduces the chances of developing preeclampsia, especially for those at high risk. For example, one study found that aspirin lowered the risk by 17%. In this trial, participants in the intervention arm will receive a daily dose of aspirin to further evaluate its effectiveness. Participants in the placebo arm will receive a placebo pill, while those in the observational arm will not receive any intervention but will be monitored. Although the amount and timing of aspirin can vary, evidence suggests it can manage preeclampsia without major side effects. Since aspirin has already been used successfully for this condition, it is generally seen as a practical choice for those at risk. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for pregnant adults aged 18-45 diagnosed with preeclampsia and expecting one baby. It's not for those planning to deliver outside the study site, involved in other trials, or with conditions like ulcers, bleeding disorders, heart disease, diabetes, kidney issues or multiple pregnancies. Also excluded are those allergic to aspirin or needing NSAIDs.

Inclusion Criteria

Diagnosed with preeclampsia

I am pregnant and between 18 and 45 years old.

Presenting for delivery with a singleton gestation.

Exclusion Criteria

Patients in labor

Co-enrolled in other trials that might affect the patients taking the study medication, as determined by the PI

I have a history of heart, lung, kidney disease, diabetes, or was pregnant with multiples.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants with elevated Activin A levels receive either aspirin therapy or placebo postpartum

6 months

1 visit (in-person) at postpartum delivery stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with measurements of GLS and other cardiac functions

6 months

1 visit (in-person) at 6 months postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Placebo

Trial Overview The trial tests if low-dose aspirin (81 mg) can lower Activin A levels postpartum and improve heart function in women with preeclampsia compared to a placebo. Participants will be randomly assigned to either the aspirin group or placebo group without knowing which they're receiving.

How Is the Trial Designed?

Group I: Intervention Arm Active Control 1 Intervention

60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of aspirin 81 mg.

Group II: Observational Arm Active Control 1 Intervention

60 subjects will be placed in the observational arm. These subjects will not receive any intervention but will be followed and asked to return at the same time interval as the other 2 groups.

Group III: Placebo Arm Placebo Group 1 Intervention

60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of a placebo pill

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study involving 898 high-risk pregnant women in China, taking 100 mg of low-dose aspirin daily did not significantly reduce the incidence of preeclampsia compared to a control group, with rates of 16.8% in the aspirin group and 17.1% in the control group.

The study also found no significant differences in adverse maternal and neonatal outcomes between the aspirin and control groups, suggesting that low-dose aspirin may not be effective for preeclampsia prevention in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China. Lin, L., Huai, J., Li, B., et al.[2022]

Low-dose aspirin has been shown to effectively reduce the risk of preeclampsia and fetal growth restriction in at-risk pregnant populations, but its benefits in low-risk groups remain unclear.

There is ongoing debate among medical organizations regarding the guidelines for aspirin use in pregnancy, with some recommending it only for at-risk women while others suggest it may be more effective and cost-efficient to prescribe it universally from the first trimester.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should we recommend universal aspirin for all pregnant women? Mone, F., Mulcahy, C., McParland, P., et al.[2022]

A higher dosage of aspirin (150 to 162 mg daily) taken in the first trimester significantly reduces the risk of preterm preeclampsia compared to a lower dosage (75 to 81 mg daily), based on a pooled analysis of 4 randomized controlled trials involving 552 participants.

While the higher dosage also showed a reduction in severe preeclampsia, it did not significantly affect the risk of term preeclampsia or all preeclampsia, indicating that while effective, the results should be interpreted cautiously due to the limited number of high-quality studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing aspirin 75 to 81 mg vs 150 to 162 mg for prevention of preterm preeclampsia: systematic review and meta-analysis. Ghesquiere, L., Guerby, P., Marchant, I., et al.[2023]

The CLASP trial indicates that while low-dose aspirin (60 mg per day) is not effective enough to recommend for widespread use in preventing pre-eclampsia, it may help reduce the risk of recurrent early onset pre-eclampsia, particularly in cases starting before 32 weeks' gestation.

Low-dose aspirin is considered safe for both pregnant mothers and their fetuses, making it a potential option for specific high-risk pregnancies, although further research is needed on other supplements like calcium and fish oil for pre-eclampsia prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-eclampsia. III: The role of aspirin in prevention. de Swiet, M.[2013]

Early initiation of low-dose aspirin (60 mg/day) before 17 weeks of pregnancy significantly reduced the risk of late-onset preeclampsia (≥34 weeks) by 29% in high-risk women, particularly those with chronic hypertension.

The study, which analyzed data from 523 women enrolled in a high-risk trial, found that aspirin led to a 41% reduction in late-onset preeclampsia rates among women with chronic hypertension, supporting the recommendation for early aspirin use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early initiation of low-dose aspirin for reduction in preeclampsia risk in high-risk women: a secondary analysis of the MFMU High-Risk Aspirin Study. Moore, GS., Allshouse, AA., Post, AL., et al.[2018]

In a study of 266 high-risk pregnant women, those who took low-dose aspirin (75 mg daily) had a significantly lower incidence of preeclampsia (10.43%) compared to those who did not take aspirin (22.52%), indicating its efficacy in prevention.

Starting low-dose aspirin before 16 weeks of gestation further enhanced its effectiveness, particularly in women without chronic hypertension, suggesting optimal timing for intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies: a retrospective real-world study in China. Xiao, Y., Ling, Q., Yao, M., et al.[2023]

Aspirin is recommended for women at risk of preeclampsia, with guidelines suggesting initiation between 11 to 28 weeks of gestation, and dosages varying from 75 mg to 150 mg depending on the level of risk.

Evidence indicates that higher doses of aspirin (greater than 100 mg daily) started before 16 weeks of gestation may be more effective in reducing the risk of preeclampsia, highlighting the need for further randomized control trials to determine optimal dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin therapy for the prevention of preeclampsia: time to reconsider our recommendations? Horgan, R., Hage Diab, Y., Waller, J., et al.[2023]

In a study of 3,597 patients at risk for preeclampsia, those taking 162 mg of aspirin had a significantly lower rate of preeclampsia (10.1%) compared to those taking the standard 81 mg dose (14.2%).

The higher 162 mg dose did not increase the risk of bleeding complications, suggesting it may be a safer and more effective option for preeclampsia prophylaxis in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Aspirin 162 mg for Preeclampsia Prophylaxis in High-Risk Patients. Ayyash, M., Goyert, G., Garcia, R., et al.[2023]

A quality improvement project in an academic OB/Gyn practice showed that implementing a standardized approach to aspirin (ASA) prescription significantly increased screening rates for preeclampsia risk from 47% to 99% among new obstetric patients.

Post-intervention, 79% of patients who screened positive received an ASA recommendation, demonstrating that the standardized process is effective and equitable, with no significant differences in recommendations based on race.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations. Gross, ME., Godecker, A., Hughes, A., et al.[2023]

A systematic review of four studies involving 392 women found that early administration of low-dose aspirin (started at or before 16 weeks of pregnancy) significantly reduces the risk of severe preeclampsia, with a relative risk of 0.22.

However, the same early aspirin treatment did not show a significant effect on reducing mild preeclampsia, indicating that while it is effective for severe cases, it may not be beneficial for milder forms of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early administration of low-dose aspirin for the prevention of severe and mild preeclampsia: a systematic review and meta-analysis. Roberge, S., Giguère, Y., Villa, P., et al.[2018]

The ASPRE trial is a large-scale, double-blind, placebo-controlled study involving 26,670 women screened for pre-eclampsia (PE), with 1,760 participants enrolled in the randomized controlled trial to test the efficacy of low-dose aspirin in preventing preterm PE.

Using a combination of maternal factors and biomarkers, the screening method can detect 75% of preterm PE cases with a 10% false-positive rate, highlighting the potential for effective early intervention with low-dose aspirin starting at 11-13 weeks of gestation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE). O'Gorman, N., Wright, D., Rolnik, DL., et al.[2019]

In a study of 932 women, low-dose aspirin (100 mg daily) significantly reduced the risk of preeclampsia and preterm birth in twin pregnancies, suggesting it may be beneficial for these high-risk pregnancies.

The use of low-dose aspirin did not increase the risk of postpartum hemorrhage, indicating it is a safe option for preventing adverse outcomes in twin pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin for primary prevention of adverse pregnancy outcomes in twin pregnancies: an observational cohort study based on propensity score matching. Ye, Y., Wen, L., Liu, X., et al.[2021]

In a study of 41 first-time pregnant women at risk for pregnancy-induced hypertension, those treated with 80 mg of aspirin daily had significantly lower rates of hypertension and preeclampsia compared to the placebo group, with no hypertensive complications in the aspirin group.

The aspirin treatment did not lead to any significant differences in pregnancy duration, birth weight, or fetal health indicators, and there was no increased risk of bleeding for mothers or babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin in primigravidae with positive roll-over test. Schröcksnadel, H., Sitte, B., Alge, A., et al.[2018]

A review of 9 studies involving nearly 13,000 pregnant women found that low-dose aspirin treatment significantly reduced the incidence of preeclampsia in 5 smaller studies, but not in 4 larger studies with over 12,000 participants.

The lack of standardized dosing, treatment duration, and risk assessment for both mother and child complicates the evaluation of low-dose aspirin's effectiveness in preventing preeclampsia, making it unclear under what conditions it may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

-Is prevention of pre-eclampsia with low dosage aspirin possible? Critical assessment of available studies-. Lippert, TH., Mück, AO.[2013]

Citations

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

Effectiveness of low-dose aspirin in reducing the risk ... Aspirin 150 mg was introduced before 11 weeks of gestation. The results showed a non-significant reduction in the incidence of 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 A meta-analysis pooling individual patient data from 31 RCTs showed a modest effect of low-dose aspirin prophylaxis on prevention of preeclampsia in groups of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211524006006

The effectiveness of low-dose aspirin for the prevention of ... Low-dose aspirin of 162 mg reduces the frequency of preeclampsia. •. Prescribe aspirin between 12 and 20 weeks and stop at 36 weeks gestational age.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2784499

Aspirin Use to Prevent Preeclampsia and Related ... Evidence demonstrates that aspirin use reduces the risk of preeclampsia in high-risk populations. Timing and Dosage. Effective dosages of low-dose aspirin range ...

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 ...