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?

This trial explores how different aspirin dosing schedules can assist pregnant women at high risk for preeclampsia and preterm birth. Researchers aim to determine whether taking aspirin once daily or splitting the dose into two is more effective for these conditions. The goal is to find the best way to use aspirin to improve the health of both mothers and babies. Women who are less than 16 weeks pregnant with one baby and have been advised to take aspirin for a high-risk pregnancy may be suitable candidates. As a Phase 1, Phase 2 trial, this research focuses on understanding aspirin's effects in people and measuring its effectiveness, offering participants a chance to contribute to important findings for maternal and infant health.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking low-dose aspirin during pregnancy can be safe for both mothers and babies. Studies indicate that it lowers the risk of preeclampsia, a serious condition during pregnancy. Importantly, low-dose aspirin does not appear to increase the risk of major problems for mothers or newborns. However, higher doses of aspirin might pose risks, such as pregnancy loss. This trial examines different ways to use aspirin to find the safest and most effective method for preventing complications in high-risk pregnancies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for high-risk pregnancies?

Researchers are excited about these aspirin treatments for high-risk pregnancies because they explore different dosing strategies that could enhance safety and effectiveness. Unlike the standard single daily dose of aspirin, which is commonly used to prevent complications like preeclampsia, this trial includes an experimental split-dose regimen. The split-dose approach, with 81mg of aspirin taken every 12 hours, might maintain more consistent blood levels, potentially offering better protection for the mother and baby. Additionally, the higher daily dose of 162mg aspirin might provide more robust preventive benefits without increasing risks. These innovative dosing strategies aim to optimize aspirin's benefits while minimizing side effects, offering hope for improved outcomes in high-risk pregnancies.

What evidence suggests that aspirin might be an effective treatment for high-risk pregnancies?

This trial will compare two dosing regimens of aspirin for high-risk pregnancies. Studies have shown that aspirin can significantly lower the risk of preeclampsia in pregnant women at high risk. Research indicates that low-dose aspirin reduces the chance of developing preeclampsia by about 17%. Evidence from several trials shows that aspirin does not increase the risk of major bleeding during pregnancy. While the effective dose for preventing preeclampsia can vary, it is important to use a consistent, low dose. These findings suggest that aspirin could improve pregnancy outcomes in high-risk women. ^{1 4 6 7 8}

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 between 16 and 55 years old.

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

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]

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]

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]

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

The optimal dosage of aspirin for preventing preeclampsia in ... The results indicate that a specific dosage of aspirin can significantly reduce the risk of preeclampsia in high‐risk pregnant women, with the most optimal ...

2. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/07/low-dose-aspirin-use-during-pregnancy

Low-Dose Aspirin Use During Pregnancy Prevention of Preeclampsia​​ The results of several small trials suggested that low-dose aspirin may be beneficial for women at high risk of preeclampsia 37 8.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04070573

Low Doses of Aspirin in the Prevention of Preeclampsia Taking ASA (as opposed to placebo) is thought to reduce the risk of preeclampsia by 17%, without increasing the risk of major obstetric bleeding. The number ...

4. 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 ...

5. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-01024-7

Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies Prophylaxis with 75 mg per day of aspirin in high-risk women resulted in a significantly lower incidence of PE than that in the control group.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12085792/

Evaluation of Low-Dose Aspirin on Pregnancy Outcomes Low-dose aspirin significantly decreases the risk of preterm and term preeclampsia but has limited impact on gestational hypertension and postpartum bleeding.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589933325001673

Maternal, fetal, and neonatal serious adverse events ... Low-dose aspirin initiated in early pregnancy is not associated with increased risks of serious adverse events for mothers, fetuses, or neonates. Evidence ...

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

Aspirin during pregnancy: Is it safe? During the first trimester, higher doses of aspirin may raise the risk of pregnancy loss. Taking a high dose also could raise the risk of a baby having ...