Aspirin for Preeclampsia

Overseen By Colleen Duncan, RN

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Chicago

Must not be taking: Nonsteroidal anti-inflammatories

Disqualifiers: Cardiomyopathy, Hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-center, double-blind, randomized, placebo-controlled clinical trial. Peripartum and postpartum Activin A are significantly elevated in women with preeclampsia. Our hypothesis is that elevated Activin A levels reflect a remediable signal and that reducing postpartum Activin A levels with aspirin therapy will improve (GLS) in preeclamptic patients.

Will I have to stop taking my current medications?

The trial requires that you do not take any nonsteroidal anti-inflammatory drugs (like ibuprofen) while participating. If you are currently taking these, you will need to stop.

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

Research shows that taking low-dose aspirin early in pregnancy can help reduce the risk of preeclampsia, a condition that can cause high blood pressure and other problems during pregnancy. Studies have found that aspirin is particularly effective for women at high risk of developing this condition. ^{1 2 3 4 5}

Is low-dose aspirin safe for pregnant women?

Low-dose aspirin (60-80 mg per day) is generally considered safe for pregnant women and their babies, with no increased risk of bleeding for the mother or fetus observed in studies. ^{6 7 8 9 10}

How does aspirin differ from other drugs for preeclampsia?

Aspirin is unique for preeclampsia prevention because it is used in low doses and its effectiveness depends on the timing and dosage, with doses over 100 mg daily before 16 weeks of pregnancy being most effective. Unlike other treatments, aspirin is widely studied and recommended by various health organizations, but guidelines on its use vary significantly. ^{6 11 12 13 14}

Eligibility Criteria

This trial is for pregnant adults aged 18-45 diagnosed with preeclampsia and expecting one baby. It's not for those planning to deliver outside the study site, involved in other trials, or with conditions like ulcers, bleeding disorders, heart disease, diabetes, kidney issues or multiple pregnancies. Also excluded are those allergic to aspirin or needing NSAIDs.

Inclusion Criteria

Diagnosed with preeclampsia

I am pregnant and between 18 and 45 years old.

Presenting for delivery with a singleton gestation.

Exclusion Criteria

Patients in labor

Co-enrolled in other trials that might affect the patients taking the study medication, as determined by the PI

I have a history of heart, lung, kidney disease, diabetes, or was pregnant with multiples.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants with elevated Activin A levels receive either aspirin therapy or placebo postpartum

6 months

1 visit (in-person) at postpartum delivery stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with measurements of GLS and other cardiac functions

6 months

1 visit (in-person) at 6 months postpartum

Treatment Details

Interventions

• Aspirin
• Placebo

Trial Overview The trial tests if low-dose aspirin (81 mg) can lower Activin A levels postpartum and improve heart function in women with preeclampsia compared to a placebo. Participants will be randomly assigned to either the aspirin group or placebo group without knowing which they're receiving.

Participant Groups

Group I: Intervention Arm Active Control 1 Intervention

60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of aspirin 81 mg.

Group II: Observational Arm Active Control 1 Intervention

60 subjects will be placed in the observational arm. These subjects will not receive any intervention but will be followed and asked to return at the same time interval as the other 2 groups.

Group III: Placebo Arm Placebo Group 1 Intervention

60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of a placebo pill

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. United States 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. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies: a retrospective real-world study in China. [2023]

4. England 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). [2019]

5. England 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. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Low-dose aspirin in primigravidae with positive roll-over test. [2018]

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

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

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

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

9. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

11. 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]

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

Low-dose aspirin therapy for the prevention of preeclampsia: time to reconsider our recommendations? [2023]

13. United States 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. [2023]

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

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