Aspirin for High-Risk Pregnancies

(DASH Trial)

Overseen By Rupsa C Boelig, MD

Age: < 65

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Thomas Jefferson University

Must be taking: Aspirin

Must not be taking: Anticoagulants

Disqualifiers: Thrombocytopenia, Bleeding disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 32 weeks gestation

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Aspirin is recommended in high risk patients to reduce the risk of preeclampsia and preterm birth, which are leading causes of both maternal and neonatal morbidity and mortality, but up to 20% will have these adverse outcomes despite therapy. Gaps in knowledge regarding pregnancy specific aspirin pharmacology and the relationship of aspirin response and pregnancy outcome, along with a lack of consensus on aspirin dosing has limited the effective use of this intervention. The investigators aim to apply principles of clinical pharmacology to determine how to optimally utilize this low cost medication to improve maternal/child health outcomes. This is a Phase I/II randomized controlled trial of high risk pregnancies recommended aspirin; participants will be randomized to take aspirin either 162mg once daily, or 81mg twice a day. Outcomes evaluated will include the difference in aspirin response between these two dosing regimens, the individual factors that impact aspirin pharmacology in pregnancy, and evaluate markers or aspirin response that may be associated with pregnancy outcome.

Will I have to stop taking my current medications?

The trial requires that you do not use any other anticoagulation medications while participating. If you are currently taking such medications, you would need to stop them to join the trial.

Is aspirin safe to use during pregnancy?

Aspirin is generally considered safe during pregnancy if the daily dose does not exceed 100mg, but there is a potential hazard, so it should not be used indiscriminately. Studies show no evidence that aspirin causes stillbirth, neonatal death, or reduced birth-weight, but caution is advised. ^{1 2 3 4 5}

How does the drug aspirin differ from other treatments for high-risk pregnancies?

Aspirin is unique in its ability to reduce the risk of preeclampsia (a pregnancy complication characterized by high blood pressure) by correcting an imbalance between thromboxane and prostacyclin, which are substances involved in blood vessel function. Unlike other treatments, low-dose aspirin is specifically targeted for women at high risk of vascular complications during pregnancy, and its use is still considered experimental with ongoing studies to confirm its safety and efficacy. ^{6 7 8 9 10}

What data supports the effectiveness of the drug aspirin for high-risk pregnancies?

Research shows that low-dose aspirin can help prevent complications like pre-eclampsia (a condition causing high blood pressure during pregnancy) and improve outcomes for pregnant women and their babies. However, it may not be effective for treating fetal growth restriction in certain cases. ^{5 11 12 13 14}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals at high risk of complications like preterm birth or preeclampsia. Participants will be those recommended to take aspirin as a preventative measure, but specifics on inclusion and exclusion criteria are not provided.

Inclusion Criteria

Singleton gestation gestational age <16 0/7 weeks, dating confirmed with ultrasound

≥1 high risk factor for preeclampsia or ≥2 moderate risk factors as per United States Preventative Services Task Force (2021)

I am recommended to take 162mg of aspirin daily during pregnancy.

Exclusion Criteria

Abnormally elevated baseline PFA-100 epinephrine closure time prior to aspirin initiation

I cannot take aspirin due to health reasons.

I am using or plan to use blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to take either 162mg aspirin daily or 81mg aspirin twice daily

Up to 32 weeks gestation

Multiple visits for monitoring and assessments

Pharmacokinetic Study

A subset of participants will be evaluated for aspirin pharmacokinetics at two dosing intervals

Concurrent with treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until delivery

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin

Trial Overview The DASH trial is testing whether taking aspirin in split doses (81mg twice daily) is more effective than a single daily dose (162mg once daily) in preventing issues such as preterm birth and preeclampsia in high-risk pregnancies.

How Is the Trial Designed?

Group I: Split dose aspirin Experimental Treatment 1 Intervention

81mg aspirin q12 hours

Group II: Daily aspirin Active Control 1 Intervention

162mg aspirin daily

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Daily treatment with 50 mg of aspirin did not prevent the rise in maternal hypertension in high-risk pregnant women, but it improved fetal blood flow and reduced the need for neonatal intensive care, indicating a potential benefit for fetal health.

Aspirin significantly inhibited thromboxane A2 production while not affecting prostacyclin levels, suggesting it may help balance the body's blood vessel regulation towards a more protective state during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. Viinikka, L., Hartikainen-Sorri, AL., Lumme, R., et al.[2019]

Aspirin is considered safe for use during pregnancy at daily doses not exceeding 100mg and has been shown to effectively prevent pre-eclampsia and fetal growth restriction in high-risk patients.

However, aspirin has not demonstrated benefits for preventing vascular placental disease in low-risk patients or for unexplained recurrent miscarriages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. Belhomme, N., Doudnikoff, C., Polard, E., et al.[2018]

In a study of 1,228 women with a history of pregnancy losses, low-dose aspirin (81 mg) was found to be well tolerated, with similar rates of possible aspirin-related symptoms and emergency care visits compared to a placebo group.

While there was a slightly higher incidence of vaginal bleeding in the low-dose aspirin group (22% vs. 17%), overall maternal and fetal complications were comparable between the aspirin and placebo groups, suggesting that low-dose aspirin is generally safe for women trying to conceive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications and Safety of Preconception Low-Dose Aspirin Among Women With Prior Pregnancy Losses. Ahrens, KA., Silver, RM., Mumford, SL., et al.[2021]

In a study of 65 pregnant women at high risk for pregnancy-induced hypertension, those treated with low-dose aspirin (100 mg daily) showed a significantly lower incidence of hypertension (11.8% vs. 35.5% in the placebo group) and pre-eclamptic toxemia (2.9% vs. 22.6%).

Aspirin treatment also corrected the imbalance between thromboxane A2 and prostacyclin metabolites, which may be a mechanism for its protective effect, with no serious side effects reported for mothers or newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. Schiff, E., Peleg, E., Goldenberg, M., et al.[2013]

Low-dose aspirin should only be used in pregnancy for specific high-risk groups, as its long-term safety is not well established.

Effective indications for low-dose aspirin include women with a history of preeclampsia leading to premature birth, those with multiple preeclampsia episodes, and women with antiphospholipid syndrome or lupus with related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[For a targeted use of aspirin]. Madar, H., Brun, S., Coatleven, F., et al.[2018]

Citations

1. Australia pubmed.ncbi.nlm.nih.gov

Neonatal outcome in a randomized, controlled trial of low-dose aspirin in high-risk pregnancies. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications. [2019]

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

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. [2019]

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

Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. [2022]

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

Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. [2022]

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

Aspirin in pregnancy: maternal and fetal effects. [2013]

7. France pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. [2018]

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

Perinatal mortality and birth-weight in relation to aspirin taken during pregnancy. [2022]

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

Complications and Safety of Preconception Low-Dose Aspirin Among Women With Prior Pregnancy Losses. [2021]

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

Which first-trimester risk assessment method for preeclampsia is most suitable? A model-based impact study. [2023]

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

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. [2013]

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

Low-dose aspirin to improve perinatal outcome. [2019]

13. France pubmed.ncbi.nlm.nih.gov

[For a targeted use of aspirin]. [2018]

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

Does low-dose aspirin initiated before 11 weeks' gestation reduce the rate of preeclampsia? [2020]