Aspirin for Preeclampsia

Overseen By Anna Reid-Stanhewicz, PHD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Aspirin, Statins, Antihypertensives

Disqualifiers: Tobacco use, Hepatic disease, Hypertension, others

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether low-dose aspirin can prevent long-term heart issues in women who experienced preeclampsia, a pregnancy complication involving high blood pressure. The study aims to determine if aspirin can repair any lasting damage to blood vessels after pregnancy. Participants will take either aspirin or a placebo daily for 12 weeks. Women who had preeclampsia in the last five years and do not have certain health issues, such as tobacco use or kidney disease, may be eligible to join. As an Early Phase 1 trial, this research focuses on understanding how aspirin works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

If you are currently taking daily aspirin, cholesterol-lowering medication, or blood pressure medication, you cannot participate in this trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

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

Research shows that low-dose aspirin is usually safe for people. Studies have found that taking low doses of aspirin can lower the risk of preeclampsia, a pregnancy complication with high blood pressure, without causing major bleeding problems. Although this trial uses aspirin after pregnancy, earlier research on using aspirin during pregnancy suggests it is safe for most people. Reports of serious side effects at these low doses are rare. Since this trial is in its early stages, it primarily aims to understand aspirin's safety for humans. While some evidence of safety exists, more detailed information will emerge as research continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for preeclampsia?

Most treatments for preeclampsia focus on managing symptoms and preventing complications, often involving medications like antihypertensives and magnesium sulfate. But aspirin is gaining attention because it might help prevent the onset of preeclampsia rather than just manage its symptoms. This trial looks at using a specific dose of aspirin, 162mg, taken once daily at bedtime, which is believed to target the condition more effectively by improving blood flow to the placenta. Researchers are excited because if successful, aspirin could offer a simple, low-cost prevention strategy for preeclampsia, potentially reducing the need for more intensive medical interventions.

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

Research has shown that a low dose of aspirin can reduce the risk of preeclampsia during pregnancy. In this trial, participants in the aspirin arm will take 162 mg of aspirin daily. Studies have found that this dosage can decrease the likelihood of developing the condition, particularly when taken between the 12th and 20th weeks of pregnancy. While most studies focus on preventing preeclampsia, aspirin may also improve blood vessel health after pregnancy, potentially lowering the risk of heart disease for women who have experienced preeclampsia. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older who had preeclampsia within the last 5 years. It's not suitable for those currently on daily aspirin, with skin diseases, using tobacco/nicotine, having liver/kidney disease, taking cholesterol or blood pressure meds, with a history of hypertension before pregnancy, gestational diabetes, currently pregnant, underweight (BMI <18.5), allergic to latex or study drugs, or with bleeding disorders and certain stomach issues.

Inclusion Criteria

Had preeclampsia in the past 5 years

Exclusion Criteria

Known allergies to study drugs

Body mass index <18.5 kg/m2

I do not have bleeding disorders, stomach ulcers, gastritis, GI bleeding, or severe acid reflux.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 162mg aspirin or placebo once daily at bedtime for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Placebo

Trial Overview The study investigates if low dose aspirin therapy after pregnancy can prevent cardiovascular disease in women who've had preeclampsia by treating lasting blood vessel damage. Participants will either receive daily aspirin treatment or a placebo to compare effectiveness.

How Is the Trial Designed?

Group I: aspirin Experimental Treatment 1 Intervention

162mg aspirin taken once daily at bedtime for 12 weeks

Group II: placebo Placebo Group 1 Intervention

placebo pill taken once daily at bedtime for 12 weeks

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?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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. 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.

3. 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 ...

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 ...

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

Low-Dose ASA for the Prevention of Preeclampsia (1) Overall, ASA prophylaxis reduces preeclampsia by about 18% (relative risk [RR] 0.82; 95% CI 0.77–0.88). (2) ASA may reduce preterm ...