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

Dose Based Aspirin Pharmacokinetics and Pharmacodynamics in Pregnancy and Association With Pregnancy Outcomes

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.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Preeclampsia
• Intervention / Treatment: Drug: Daily aspirin (ASA); Drug: Split dose aspirin (ASA)

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 Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rupsa C Boelig, MD; Phone Number: 215-955-5000; Email: rupsa.boelig@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19060
      • Recruiting
      • Thomas Jefferson University
      • Contact: Rupsa C Boelig, MD; Phone Number: 215-955-5000; Email: rupsa.boelig@jefferson.edu
      • Contact: Brandy Firman; Email: brandy.firman@jeffereson.edu
      • Principal Investigator: Rupsa C Boelig, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Daily aspirin; 162mg aspirin daily	Drug: Daily aspirin (ASA); 162mg aspirin taken daily
Experimental: Split dose aspirin; 81mg aspirin q12 hours	Drug: Split dose aspirin (ASA); 81mg aspirin q12hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspirin Response PFA-100 epinephrine closure time (seconds)	Difference in PFA-100 epinephrine closure time (seconds)	2-4 weeks after aspirin initiation

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): February 14, 2025

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Aspirin; Randomized clinical trial; Pregnancy; Pharmacokinetics; Phase I/II; Pharmacodynamics; Preeclampsia; Preterm birth
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Premature Birth; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Aspirin
• Other Study ID Numbers: IRISID-2024-1554; 1R01HD112076 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be submitted to NICHD DASH and can be requested through NICHD DASH
• IPD Sharing Time Frame: 1 year after study completion
• IPD Sharing Access Criteria: Data will be submitted to NICHD DASH and may be requested through DASH
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No