Aspirin for Preeclampsia Prevention

Overseen by Amihai Rottenstreich, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Rockefeller University

Must be taking: Low-dose aspirin

Must not be taking: Antithrombotics, NSAIDs

Disqualifiers: Chronic hypertension, Diabetes, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing low-dose aspirin to prevent preeclampsia in pregnant women, especially Black women who may have higher rates of aspirin failure. Aspirin works by preventing blood clots and improving blood flow in the placenta. Low-dose aspirin has been studied for a long time for its potential to prevent preeclampsia, with mixed results.

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.

What data supports the effectiveness of the drug aspirin for preventing preeclampsia?

Research shows that starting low-dose aspirin early in pregnancy can help prevent preeclampsia, especially when begun before 16 weeks of gestation. Recent studies and reviews suggest it reduces the risk of early-onset preeclampsia and related complications. ^{1 2 3 4 5}

Is low-dose aspirin safe for preventing preeclampsia?

Low-dose aspirin appears to be safe for pregnant women, their babies, and newborns, based on studies involving over 13,000 women. ^{1 6 7 8 9}

How is aspirin different from other drugs for preventing preeclampsia?

Aspirin is unique in its ability to prevent preeclampsia by inhibiting the production of thromboxane, a substance that can be elevated in severe cases of the condition. It is most effective when started early in pregnancy, before 16 weeks, and is considered safe for both the mother and fetus at low doses. ^{3 4 5 8 10}

Research Team

Amihai Rottenstreich, MD

Principal Investigator

Rockefeller University

Eligibility Criteria

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

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.

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

Exclusion Criteria

I have had a bleeding stroke in the past.

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

I have had kidney or liver problems.

Trial Timeline

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

Treatment Details

Interventions

• Aspirin (Antiplatelet agent)

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.

Participant Groups

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 Canada, China for the following indications:

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+

Richard P. Lifton

Rockefeller University

Chief Executive Officer since 2016

MD, PhD

Barry S. Coller

Rockefeller University

Chief Medical Officer since 2016

MD

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

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

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

2. United States 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. [2018]

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

Aspirin vs Heparin for the Prevention of Preeclampsia. [2018]

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

Efficacy and Safety of Aspirin 162 mg for Preeclampsia Prophylaxis in High-Risk Patients. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations. [2023]

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

Low-dose aspirin therapy in obstetrics. [2019]

7. Portugal pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Aspirin for Prevention of Preeclampsia. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Pre-eclampsia. III: The role of aspirin in prevention. [2013]