Aspirin for Preeclampsia Prevention

Overseen By Amihai Rottenstreich, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Rockefeller University

Must be taking: Low-dose aspirin

Must not be taking: Antithrombotics, NSAIDs

Disqualifiers: Chronic hypertension, Diabetes, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low-dose aspirin can prevent preeclampsia, a serious pregnancy complication involving high blood pressure. Researchers aim to understand why aspirin sometimes fails and explore if certain genes might influence its effectiveness. The trial includes two groups: women who previously had preeclampsia and took aspirin in a later pregnancy, and healthy volunteers for comparison. Potential participants include women with a history of preeclampsia who took low-dose aspirin in a subsequent pregnancy. As an Early Phase 1 trial, this research focuses on understanding how low-dose aspirin works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires participants to stop taking non-prescription NSAIDs (like ibuprofen) for one week before certain tests. If you are currently using antithrombotic agents (like aspirin or warfarin), you cannot participate in the trial.

Is there any evidence suggesting that aspirin is likely to be safe for humans?

Research shows that a low dose of aspirin is generally safe for pregnant individuals aiming to prevent preeclampsia. Studies have found that taking 81 mg of aspirin daily can reduce the risk of this condition by about 17% without significantly increasing the chance of major bleeding during pregnancy. This dose is often recommended for those at high risk of developing preeclampsia, a serious pregnancy issue involving high blood pressure.

Aspirin is already used for other health conditions and is well understood. Evidence supports its safety during pregnancy, showing it is usually well-tolerated in low doses. Some individuals might experience mild side effects, but serious problems are rare. Overall, aspirin has a good track record for preventing preeclampsia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Aspirin is unique because it offers a simple, low-cost approach to potentially preventing preeclampsia, a serious pregnancy complication. Unlike other treatments that may involve more complex interventions, aspirin works by thinning the blood and improving blood flow to the placenta, which may help reduce the risk of developing preeclampsia. Researchers are excited about this treatment because its widespread availability and low side-effect profile make it an accessible option for many pregnant women, particularly those with a history of preeclampsia. Additionally, its use in an enteric-coated form helps minimize gastric irritation, enhancing patient comfort.

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

Research has shown that low-dose aspirin can help prevent preeclampsia, a serious pregnancy complication. Studies have found that aspirin can reduce the risk of developing preeclampsia by 10-20%, particularly in women at high risk. In this trial, women with a prior history of preeclampsia will receive a single dose of enteric-coated 81 mg aspirin. Taking aspirin has not been linked to an increased risk of major bleeding during pregnancy. ^{2 5 6 7 8}

Who Is on the Research Team?

Amihai Rottenstreich, MD

Principal Investigator

Rockefeller University

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 who had preeclampsia in a past pregnancy, took low-dose aspirin before the 16th week of their next pregnancy with at least 80% compliance, and did not have significant health issues like bleeding disorders or chronic hypertension. It's not for those currently pregnant or on blood thinners.

Inclusion Criteria

Aspirin was given in their subsequent pregnancy in a 81 mg dose prior to 16 weeks of gestation, and was taken with a self-reported compliance rate of at least 80%

Subsequent pregnancy lasted beyond 20 weeks of gestation

I am a woman aged 18-45 with a history of preeclampsia and took low dose aspirin in my next pregnancy, regardless of preeclampsia recurrence.

Exclusion Criteria

Participants may be excluded at the discretion of the investigator for medical, psychological or other reasons

I have had a bleeding stroke in the past.

I have had kidney or liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of enteric-coated 81 mg aspirin to assess platelet response and genetic factors associated with aspirin failure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for platelet response and thromboxane A2 levels at baseline and 1 hour post aspirin administration

1 day

1 visit (in-person)

Genetic Analysis

Allelic frequency of the PAR4 variant (rs773902) is analyzed in relation to aspirin success in preeclampsia prevention

At study enrollment

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin

Trial Overview The study looks into why low-dose aspirin sometimes fails to prevent preeclampsia in pregnant women. Researchers are examining genetic factors that might affect how well aspirin works to reduce this risk.

How Is the Trial Designed?

Group I: Women with prior history of preeclampsia who received aspirin in subsequent gestation Experimental Treatment 1 Intervention

Single-dose of enteric-coated 81 mg aspirin

Group II: Healthy volunteers Active Control 1 Intervention

In this group, no aspirin will be given, as blood draw will not be performed at all among the healthy volunteers. The group of healthy volunteers will serve only for the SNP assay development.

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?

Rockefeller University

Lead Sponsor

Trials

162

Recruited

16,700+

Published Research Related to This Trial

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]

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]

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]

Low-dose aspirin has been shown to effectively prevent preeclampsia in high-risk pregnant individuals, particularly those with a history of the condition, according to large meta-analyses of individual patient data.

Despite the evidence supporting its use, guidelines for aspirin's application in preventing preeclampsia vary widely across countries, with ongoing debates about screening methods, target populations, and appropriate dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin for Prevention of Preeclampsia. Atallah, A., Lecarpentier, E., Goffinet, F., et al.[2019]

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]

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]

Aspirin use during pregnancy has been shown to significantly reduce the risk of developing preeclampsia, a serious condition that can lead to complications for both the mother and baby.

The systematic review analyzed updated evidence and supports the recommendation for aspirin as a preventive measure, highlighting its safety and efficacy in reducing related morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

More evidence for low-dose aspirin in preventing pre-eclampsia. [2022]

Low-dose aspirin, when started before 16 weeks of gestation, has been associated with a reduction in early-onset preeclampsia and lower rates of perinatal death or morbidity, making it a promising preventive treatment.

Heparin may also help prevent preeclampsia due to its antithrombotic and anti-inflammatory properties, but studies show mixed results regarding its effectiveness, indicating more research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin vs Heparin for the Prevention of Preeclampsia. Katsi, V., Kanellopoulou, T., Makris, T., et al.[2018]

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]

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]

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 Systematic reviews of low-dose aspirin when used in the setting of preeclampsia prevention have consistently reported a 10–20% reduction in fetal growth ...

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. 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 ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32835720/

Prevention of preeclampsia with aspirin The first possible link between the use of aspirin and the prevention of preeclampsia was suggested by a case report published in 1978, followed ...

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 ... Pregnant persons at high risk for preeclampsia, The USPSTF recommends the use of low-dose aspirin (81 mg/day) as preventive medication after 12 ...

8. psbchealthhub.ca psbchealthhub.ca/clinical-guidance/816

Low-Dose ASA for the Prevention of Preeclampsia | PHSA Hub Low-dose acetylsalicylic acid (ASA), ideally started at 11 to 16 weeks gestational age, can help reduce the risk of preeclampsia for women/people at elevated ...