Aspirin for Pre-eclampsia

Overseen By Aleha Aziz, MD, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: Aspirin, Anticoagulants, NSAIDs

Disqualifiers: Nasal polyps, GI bleeding, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use aspirin or certain blood thinners (like Lovenox or heparin) postpartum for other reasons. If you have any allergies to aspirin or similar drugs, you should not participate.

What data supports the effectiveness of the drug aspirin for pre-eclampsia?

Research shows that low-dose aspirin can improve symptoms of pre-eclampsia, such as high blood pressure and swelling, and may reduce the risk of developing the condition, especially when started early in high-risk pregnancies. ^{1 2 3 4 5}

Is low-dose aspirin safe for use in pregnancy, particularly for preventing pre-eclampsia?

Research indicates that low-dose aspirin is generally safe for pregnant women, their babies, and newborns, although there may be a small risk of bleeding complications. It has been used in studies involving thousands of women and is considered safe when used as recommended. ^{3 6 7 8 9}

How is aspirin used to prevent pre-eclampsia different from other treatments?

Aspirin is unique in preventing pre-eclampsia because it works by inhibiting the production of thromboxane, a substance that is elevated in severe cases of the condition. Low-dose aspirin is considered safe for pregnant women and their babies, and it may be particularly effective in reducing the risk of early onset pre-eclampsia. Other potential treatments like calcium supplements and fish oil need more research, and diuretics and salt reduction are not recommended. ^{1 3 10 11 12}

What is the purpose of this trial?

The purpose of this research study is to find out whether women with severe preeclampsia taking low-dose aspirin (LDA) for 3 weeks post-delivery will experience an improvement in endothelial function (measured as flow-mediated dilation - FMD) and severity of disease, as the effects of preeclampsia can persist postpartum. Women diagnosed with severe preeclampsia prior to delivery will be enrolled and randomized to receive either low-dose aspirin (81mg) or placebo to take daily for up to 3 weeks post-delivery. Exploratory objective includes healthy control postpartum patients without preeclampsia and not on LDA during pregnancy or postpartum in comparison with the primary study population affected by preeclampsia with severe features.

Research Team

Aleha Aziz, MD, MPH

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for women over the age of 18 who were diagnosed with severe preeclampsia before giving birth, regardless of whether they had a single or multiple pregnancy and were at least 20 weeks into their pregnancy. It's not open to those who don't meet these criteria.

Inclusion Criteria

You have been diagnosed with severe preeclampsia before giving birth.

You are either pregnant with one baby or multiple babies.

You are at least 20 weeks pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose aspirin (81mg) or placebo daily for up to 3 weeks postpartum

3 weeks

Follow-up

Participants are monitored for changes in endothelial function and blood pressure after treatment

3 weeks

Treatment Details

Interventions

• Aspirin
• Placebo

Trial Overview The study is testing if taking low-dose aspirin (81mg) daily for three weeks after delivery helps improve blood vessel function and reduces disease severity in women with severe preeclampsia, compared to a placebo.

Participant Groups

Group I: Healthy Controls Group Active Control 1 Intervention

Subjects who are healthy volunteers (n = 10) without severe preeclampsia prior to delivery.

Group II: Low-Dose Aspirin (LDA) Intervention Group Active Control 1 Intervention

Subjects diagnosed with severe preeclampsia prior to delivery (antepartum or intrapartum) will take 81mg of aspirin daily for up to 3 weeks postpartum, starting within 4 days after delivery.

Group III: Placebo Control Group Placebo Group 1 Intervention

Subjects diagnosed with severe preeclampsia prior to delivery (antepartum or intrapartum) will take placebo oral capsule daily for up to 3 weeks postpartum, starting within 4 days after delivery.

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?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Findings from Research

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 treatment in pre-eclamptic women resulted in more significant improvements in blood pressure, temperature, edema, and albuminuria compared to conventional therapy, suggesting its efficacy in managing severe pre-eclampsia.

Both treatment groups had similar obstetric progress and perinatal outcomes, indicating that while low-dose aspirin may enhance certain clinical parameters, it does not negatively impact overall pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of severe pre-eclampsia by acetyl salicylic acid. Toppozada, M., Khowessah, M., Shaala, S., et al.[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 of 164 women with pre-existing diabetes, aspirin did not significantly reduce the risk of pre-eclampsia compared to those not receiving aspirin, suggesting limited efficacy in this specific population.

However, aspirin use was associated with a higher risk of postpartum hemorrhage, indicating a potential safety concern, while early pregnancy HbA1c levels were identified as a useful tool for assessing pre-eclampsia risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin and pre-eclampsia prevention in women with pre-existing diabetes: a retrospective study. Lah, S., Cheung, NW., Lee, V., et al.[2021]

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 71,627 singleton pregnancies, low-dose aspirin (LDA) was associated with a higher risk of placental abruption (adjusted odds ratio of 1.44) and postpartum hemorrhage (PPH) (adjusted odds ratio of 1.21), suggesting potential safety concerns with its use during pregnancy.

Despite its recommendation for preventing preterm pre-eclampsia, the findings indicate that LDA may not be suitable for all pregnancies, particularly without further research into its bleeding risks, especially in lower-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propensity score analysis of low dose aspirin and bleeding complications in pregnancy. Souter, V., Painter, I., Sitcov, K., et al.[2023]

A combined multimarker screening strategy in the first trimester can effectively identify 96% of early preterm pre-eclampsia cases and 77% of preterm pre-eclampsia cases, significantly improving detection rates compared to traditional risk factor approaches.

Administering 150 mg of aspirin at bedtime to women identified as high-risk for pre-eclampsia has been shown to significantly reduce the incidence of both preterm and early pre-eclampsia, with minimal adverse effects for mothers and babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-eclampsia screening in the first trimester - preemptive action to prevent the peril. Vikraman, SK., Elayedatt, RA.[2022]

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 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]

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]

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]

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]

References

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

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

2. Japan pubmed.ncbi.nlm.nih.gov

Treatment of severe pre-eclampsia by acetyl salicylic acid. [2019]

3. Portugal pubmed.ncbi.nlm.nih.gov

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

4. Australia pubmed.ncbi.nlm.nih.gov

Aspirin and pre-eclampsia prevention in women with pre-existing diabetes: a retrospective study. [2021]

5. 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]

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

Propensity score analysis of low dose aspirin and bleeding complications in pregnancy. [2023]

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

Pre-eclampsia screening in the first trimester - preemptive action to prevent the peril. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Low-dose aspirin therapy in obstetrics. [2019]

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

The pharmacological prevention of pre-eclampsia. [2019]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

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

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

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