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

Trial Summary

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.

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

Research shows that low-dose aspirin can help prevent preeclampsia in women who are at high risk. It is considered safe for both the mother and baby, and it works by balancing certain chemicals in the body that are linked to preeclampsia. ^{1 2 3 4 5}

Is low-dose aspirin safe for pregnant women and their babies?

Research shows that low-dose aspirin is generally safe for pregnant women and their babies, with studies involving over 13,000 women indicating no significant safety concerns. ^{1 2 4 6 7}

How does low-dose aspirin differ from other drugs for preeclampsia?

Low-dose aspirin is unique in its ability to selectively inhibit thromboxane, a substance that increases blood pressure and reduces blood flow to the placenta, without significantly affecting prostacyclin, which promotes blood flow and reduces blood pressure. This makes it particularly effective in preventing preeclampsia in high-risk pregnancies, and it is considered safe for both the mother and fetus. ^{1 3 4 8 9}

What is the purpose of this trial?

Preeclampsia is a pregnancy disorder affecting \~5-10% of pregnancies in the United States. Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. Low dose aspirin (LDA; 75-150mg/daily) is currently the most effective and clinically accepted therapy for reducing preeclampsia prevalence in women at high risk for developing the syndrome. The purpose of this study is to interrogate the mechanisms by which LDA therapy mitigates persistent vascular dysfunction in postpartum women who have had preeclampsia. In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) they examine the blood vessels in a dime-sized area of the skin in women who have had a history of preeclampsia. As a compliment to these measurements, they also draw blood from the subjects and isolate the inflammatory cells.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. 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]

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

Should we recommend universal aspirin for all pregnant women? [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Low-dose aspirin therapy in obstetrics. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

The pharmacological prevention of pre-eclampsia. [2019]