Low Dose 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, 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: 1

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how low-dose aspirin reduces blood vessel issues in women who experienced preeclampsia, a pregnancy-related disorder. Researchers will examine aspirin's effects on small blood vessels in the skin and analyze blood samples for signs of inflammation. Eligible participants include women who are 12 weeks to 5 years postpartum and have had either preeclampsia or a normal pregnancy, regardless of aspirin use during pregnancy. As an Early Phase 1 trial, this research focuses on understanding aspirin's effects in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you stop taking daily aspirin, statins, cholesterol-lowering medications, and antihypertensive medications to participate.

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

Research has shown that low-dose aspirin is generally safe during pregnancy. Specifically, doses between 75 and 150 mg per day have been used to help prevent preeclampsia, a condition affecting some pregnant women. Studies suggest starting low-dose aspirin between 12 and 28 weeks of pregnancy for those at high risk of developing this condition.

Although safety data for doses up to 150 mg per day is limited, experts agree that low-dose aspirin is usually well-tolerated. Higher doses of aspirin are generally not recommended during pregnancy due to potential risks. Overall, low-dose aspirin is widely accepted and used for preventing preeclampsia, with few side effects reported in studies. ^{1 2 3 4 5}

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

Researchers are excited about the use of low-dose aspirin for preeclampsia because it offers a potentially safer and more accessible option compared to current treatments, which often involve more intensive interventions like antihypertensive medications or early delivery. Aspirin is unique in its ability to improve microvascular function by influencing blood flow and reducing inflammation, which are crucial factors in managing preeclampsia. This approach could lead to better outcomes for both mothers and babies, making it a promising area of study.

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

Research has shown that taking low-dose aspirin can lower the risk of preeclampsia, a condition that can occur during pregnancy. Studies have found that aspirin can reduce the chance of developing preeclampsia by 34% when taken correctly. The best results come from taking 75-150 mg daily. Evidence also suggests that starting aspirin before 20 weeks of pregnancy is most effective. Although the exact mechanism of aspirin is not fully understood, it is believed to reduce inflammation and improve blood flow. Overall, low-dose aspirin is considered a reliable option for women at high risk of preeclampsia. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older who are 12 weeks to 5 years postpartum. It's suitable for those with a history of normal pregnancy or preeclampsia, regardless of low dose aspirin use during pregnancy. Women currently on daily aspirin, with skin diseases, tobacco use, certain chronic diseases like reduced kidney function, using cholesterol medications or antihypertensives, prior hypertension or gestational diabetes, current pregnancy, underweight BMI (<18.5), or allergies to study materials and drugs cannot participate.

Inclusion Criteria

I used low-dose aspirin during a normal pregnancy.

I had preeclampsia and did not take low-dose aspirin during my pregnancy.

12 weeks to 5 years postpartum

Exclusion Criteria

Current pregnancy

I have a liver, metabolic condition, or kidney disease with reduced kidney function.

I take aspirin every day.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo assessment of microvascular function using intradermal microdialysis and blood draws to isolate inflammatory cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin

Trial Overview The study investigates how low dose aspirin therapy affects blood vessel function after childbirth in women who had preeclampsia. Researchers will examine the microvascular function in the skin using intradermal microdialysis to deliver Acetylcholine and Endothelin-1 locally and analyze inflammatory cells from drawn blood.

How Is the Trial Designed?

Group I: assessment of microvascular function Experimental Treatment 2 Interventions

The investigators use intradermal microdialysis to deliver acetylcholine, acetylcholine + L-NAME, endothelin-1, endothelin-1 + BQ-788, and endothelin-1 + BQ-123 to the cutaneous microvasculature.

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

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]

Low-dose aspirin therapy can effectively reduce the risk of preterm preeclampsia when started before 16 weeks of gestation and at doses greater than 100 mg/day, as shown in meta-analyses of clinical trials.

Despite its benefits in correcting placental imbalances and reducing oxidative stress, some women still develop preeclampsia, potentially due to factors like altered sphingolipids and other mechanisms not influenced by aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta. Walsh, SW., Strauss, JF.[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]

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 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]

Low-dose aspirin during pregnancy is considered safe and may help correct the imbalance of vascular factors associated with preeclampsia, particularly by reducing sensitivity to angiotensin II.

Clinical trials suggest that low-dose aspirin can effectively lower the risk of preeclampsia and fetal growth retardation in high-risk women, but ongoing large trials are needed to confirm its overall effectiveness and safety for broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin in the prevention of preeclampsia and fetal growth retardation: rationale, mechanisms, and clinical trials. Dekker, GA., Sibai, BM.[2019]

Low-dose aspirin (60 to 81 mg/day) effectively reduces thromboxane production in preeclamptic women, which helps alleviate symptoms by promoting vasodilation and increasing uteroplacental blood flow without significantly affecting prostacyclin levels.

Clinical studies show that low-dose aspirin therapy not only decreases the incidence of preeclampsia but also does not appear to harm the fetus, making it a promising treatment option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin: treatment for the imbalance of increased thromboxane and decreased prostacyclin in preeclampsia. Walsh, SW.[2022]

Low-dose aspirin can reduce the incidence of pre-eclampsia by about 25%, particularly in high-risk patients, and should ideally be started between 10-14 weeks of pregnancy for maximum effectiveness.

The use of low-dose aspirin is considered safe for both the fetus and neonate, with minimal risk of complications such as abruptio placentae, but further research is needed to optimize treatment strategies and explore combinations with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacological prevention of pre-eclampsia. Dekker, GA.[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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11088435/

The optimal dosage of aspirin for preventing preeclampsia in ... The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect ...

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

4. 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.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5681618/

Aspirin for Prevention of Preeclampsia - PMC Safety data at 150 mg/day are still limited. Aspirin, in primary prevention of preeclampsia, given to high-risk patients identified in the ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2589933323001428

Aspirin 75-81mg vs 150-162mg: Preeclampsia Prevention An aspirin dosage of 150 to 162 mg daily was associated with a lower risk of preterm PE than an aspirin dosage of 75 to 81 mg daily.

8. uspreventiveservicestaskforce.org uspreventiveservicestaskforce.org/uspstf/recommendation/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

Aspirin for Preeclampsia Prevention: Recommendation For pregnant persons: Prescribe low-dose (81 mg/d) aspirin after 12 weeks of gestation to persons who are at high risk for preeclampsia.

9. mayoclinic.org mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/aspirin-during-pregnancy/faq-20058167

Aspirin during pregnancy: Is it safe? Low-dose aspirin is safe to use throughout pregnancy, and it may be recommended in some situations. Higher doses of aspirin typically are not recommended ...