Clinical trial NCT06826859: Daily Aspirin vs Split Dosing in High-risk Pregnancies (DASH)
Official title: Dose Based Aspirin Pharmacokinetics and Pharmacodynamics in Pregnancy and Association With Pregnancy Outcomes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Preterm Birth
Preeclampsia
Keywords: Aspirin
Preeclampsia
Preterm birth
Pregnancy
Pharmacokinetics
Pharmacodynamics
Phase I/II
Randomized clinical trial
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2025-02-14
Enrollment: 400
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Aspirin Response PFA-100 epinephrine closure time (seconds)
timeFrame: 2-4 weeks after aspirin initiation
Secondary outcomes:
measure: Aspirin response (PFA-100 epinephrine closure time)
timeFrame: 28-32 weeks gestation
measure: Urinary thromboxane concentration
timeFrame: 2-4 weeks after aspirin initiation
measure: Urinary Thromboxane concentration
timeFrame: 28-32 weeks gestation
measure: Inadequate aspirin response
timeFrame: 2-4 weeks after aspirin initiation
measure: Inadequate aspirin response
timeFrame: 28-32 weeks gestation
measure: Preterm birth
timeFrame: Delivery
measure: Indicated preterm birth
timeFrame: delivery
measure: Spontaneous preterm birth
timeFrame: delivery
measure: MicroRNAs
timeFrame: 2-4 weeks after aspirin initiation
measure: MicroRNAs
timeFrame: 28-32 weeks gestation
measure: Placental histopathology
timeFrame: Delivery
measure: Birthweight
timeFrame: Delivery
measure: Fetal growth restriction
timeFrame: delivery
measure: Hypertensive disorder of pregnancy
timeFrame: delivery
measure: Gestational age at delivery
timeFrame: Delivery
measure: Pregnancy loss<20 weeks
timeFrame: delivery
measure: Fetal demise
timeFrame: delivery
measure: Antepartum bleeding
timeFrame: Delivery
measure: Abruption
timeFrame: delivery
measure: Placental hematoma
timeFrame: delivery
measure: Postpartum hemorrhage
timeFrame: Delivery
measure: Adherence
timeFrame: 2-4 weeks after aspirin
measure: Adherence
timeFrame: 28-32 weeks
measure: Neonatal intraventricular hemorrhage Grade II or higher
timeFrame: Neonatal discharge
measure: Cordblood serum thromboxane
timeFrame: Delivery
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
References: