Daily Aspirin vs Split Dosing in High-risk Pregnancies (DASH)

Thomas Jefferson University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Preeclampsia; Preterm Birth

Treatments: Drug: Split dose aspirin (ASA); Drug: Daily aspirin (ASA)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06826859

IRISID-2024-1554

1R01HD112076 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

This is an unblinded randomized controlled Phase I/II trial comparing high risk singleton pregnancies randomized to 162mg daily (daily dose) vs 81mg q12hours (split dose). Participants will be enrolled prior to 16 weeks gestation. The primary outcome is platelet inhibition as assessed by PFA-100 epinephrine closure time, assessed 2-4 weeks after initiation and again at 28-32 weeks gestation. A subset of participants will be enrolled in a pharmacokinetic study to evaluate pharmacokinetics of aspirin in pregnancy at the two dosing intervals. Secondary outcomes include urine thromboxane at each visit, platelet associated microRNAs. Individual factors associated with aspirin pharmacokinetics and pharmacodynamics in pregnancy will be assessed. Finally, the relationship between these pharmacodynamic markers and pregnancy outcome will be evaluated.

Enrollment: 400 estimated patients

Sex: Female

Ages: 16 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)
• Recommendation for 162mg aspirin daily in pregnancy
• Age 16-55 years old

Exclusion criteria

• Contraindication to aspirin
• Current or planned use of any other anticoagulation
• Thrombocytopenia, other known platelet or bleeding disorder
• Abnormally elevated baseline PFA-100 epinephrine closure time prior to aspirin initiation

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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400 participants in 2 patient groups

Daily aspirin

Active Comparator group

Description:

162mg aspirin daily

Treatment:

Drug: Daily aspirin (ASA)

Split dose aspirin

Experimental group

Description:

81mg aspirin q12 hours

Treatment:

Drug: Split dose aspirin (ASA)