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

Phase 1

Not yet recruiting

• Conditions: Preterm Birth; Preeclampsia
• Interventions: Drug: Daily aspirin (ASA); Drug: Split dose aspirin (ASA)

• Registration Number: NCT06826859
• Lead Sponsor: Thomas Jefferson University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2025-01-28
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-12
• Last Update Submitted: 2025-02-12
• Study First Posted: 2025-02-14
• Last Update Posted: 2025-02-14
• Study Start: 2025-03-01
• Primary Completion: 2029-07-01
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 400

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Daily aspirin	Daily aspirin (ASA)	162mg aspirin daily
Split dose aspirin	Split dose aspirin (ASA)	81mg aspirin q12 hours

Primary Outcome Measures

Name	Time	Method
Aspirin Response PFA-100 epinephrine closure time (seconds)	2-4 weeks after aspirin initiation	Difference in PFA-100 epinephrine closure time (seconds)

Secondary Outcome Measures

Name	Time	Method
Aspirin response (PFA-100 epinephrine closure time)	28-32 weeks gestation	Difference in PFA-100 epinephrine closure time (seconds)
Urinary thromboxane concentration	2-4 weeks after aspirin initiation	Difference in Urine thromboxane (AspirinWorks)
Urinary Thromboxane concentration	28-32 weeks gestation	Difference in Urinary thromboxane (AspirinWorks)
Inadequate aspirin response	28-32 weeks gestation	Number of participants with PFA-100 epinephrine closure time\<150seconds
Preterm birth	Delivery	Number of participants with Preterm birth\<37 weeks
Indicated preterm birth	delivery	Number of participants with Preterm birth\<37 weeks due to preeclampsia or fetal growth restriction
Spontaneous preterm birth	delivery	Number of participants with spontaneous preterm birth \<37 weeks
MicroRNAs	28-32 weeks gestation	Fold-change from baseline for concentration of circulating microRNAs
Placental histopathology	Delivery	Placental pathology per Amsterdam criteria. Number of participants with maternal vascular malperfusion, intervillous thrombosis
Birthweight	Delivery	Infant birthweight (grams)
Fetal growth restriction	delivery	Number of participants diagnosed with Fetal growth restriction
Hypertensive disorder of pregnancy	delivery	Number of participants diagnosed with Preeclampsia or gestational hypertension
Gestational age at delivery	Delivery	Gestational age at delivery (weeks)
Pregnancy loss<20 weeks	delivery	Number of participants with Pregnancy loss (delivery, demise, miscarriage)\<20 weeks gestation
Fetal demise	delivery	Number of participants with Fetal demise diagnosed \>=20 weeks gestation
Antepartum bleeding	Delivery	Number of participants with any admission for antepartum bleeding
Abruption	delivery	Number of participants with Abruption diagnosed prior to or at delivery
Placental hematoma	delivery	Number of participants with Placental hematoma suspected on ultrasound
Postpartum hemorrhage	Delivery	Number of participants with Postpartum hemorrhage \>1000ml
Adherence	28-32 weeks	Number of participants with Adherence\>75%
Neonatal intraventricular hemorrhage Grade II or higher	Neonatal discharge	Number of participants with infants found to have Neonatal IVH grade II or higher diagnosed on ultrasound post natally
Cordblood serum thromboxane	Delivery	cordblood serum thromboxane concentration

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States