Higher-dose versus standard-dose aspirin to prevent another early preterm birth

A Dose Escalation Study of Low Dose Aspirin for the Prevention of Recurrent Preterm Birth

This trial tests whether taking 162 mg daily aspirin instead of 81 mg, starting at 10–15 weeks of pregnancy, helps people with a prior early preterm birth avoid another preterm delivery or fetal death before 35 weeks.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1800 (estimated)
• Ages: 14 Years and up
• Sex: Female
• Sponsor: The George Washington University Biostatistics Center (Academic / other)
• Locations: 14 sites (Birmingham, Alabama and 13 other locations)
• Trial ID: NCT06980025 on ClinicalTrials.gov

What this trial studies

This phase III, multicenter, double-blind randomized trial will enroll 1,800 pregnant individuals with a prior preterm birth before 35 weeks and randomize them to 162 mg or 81 mg of aspirin daily. Study drug is started between 10 and 15 weeks gestation and continued through 36 weeks, 6 days, with participants and staff blinded to dose. The primary outcome is recurrent preterm delivery or fetal death before 35 weeks, while secondary outcomes include ischemic placental disease and other maternal and neonatal complications. Safety data and exploratory subgroup analyses will be collected across several U.S. academic centers.

Who should consider this trial

Good fit: Ideal candidates are pregnant people aged 14 or older with a singleton pregnancy who had a prior spontaneous preterm birth, ischemic placental disease, or stillbirth between 20 and 34 weeks and who can be randomized between 10+0 and 15+6 weeks gestation.

Not a fit: People without a prior qualifying preterm birth, those with multifetal pregnancies, or those with contraindications such as known aspirin allergy are unlikely to benefit from this aspirin dose comparison.

Why it matters

Potential benefit: If successful, a higher daily aspirin dose could lower the chance of recurrent early preterm birth and related fetal deaths, improving outcomes for both mothers and babies.

How similar studies have performed: Lower-dose aspirin has shown benefit for preeclampsia prevention in some settings, but using a higher 162 mg dose specifically to prevent recurrent early preterm birth is relatively novel with limited large-scale prior evidence.

Eligibility criteria

Inclusion Criteria:

* 14 years or older
* Singleton gestation. Twin gestation reduced to a singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher-order multifetal gestations reduced to singletons are not eligible.
* Gestational age at randomization between 10 weeks 0 days and 15 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
* Prior preterm birth between 20 weeks 0 days and 34 weeks 6 days with one of the following in the proximal birth reaching 20 weeks or greater:

  * Spontaneous preterm birth is defined as spontaneous preterm labor or premature rupture of membranes
  * Ischemic placental disease is defined as preeclampsia, small for gestational age, fetal growth restriction, or placental abruption, as defined clinically.
  * Stillbirth excluding those with known genetic disorders or major congenital anomalies.

Exclusion Criteria:

* Known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., history of peptic ulcer disease, nasal polyps, NSAID-induced asthma, history of gastrointestinal bleeding, known G6PD deficiency, severe hepatic dysfunction, bleeding disorders, and consumption of 3 or more alcoholic drinks per day)
* Taking other anticoagulants such as Heparin or Low-Molecular weight Heparin
* Thrombocytopenia defined as a platelet count defined as a platelet count \<100,000 microliters
* Gastric bypass surgery, regardless of type
* Aspirin use \>81 mg daily during the current pregnancy who are not willing or able to go through a 2-week washout before randomization.
* Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery.
* Known fetal genetic disease or major malformations
* Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from twins to singleton, is not an exclusion.
* Any fetal/maternal condition requiring invasive in-utero assessment or treatment, for example, significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia.
* Patients with any of the following medical conditions because of increased risk for adverse pregnancy outcome or indicated preterm birth:

  * Treated hypertension requiring more than one agent
  * Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL
  * Conditions treated with chronic oral glucocorticoid therapy (e.g., systemic lupus erythematosus)
  * Uncontrolled hyper- and hypothyroid disease
  * New York Heart Association (NYHA) stage II or greater cardiac disease
* Planned indicated delivery prior to 37 weeks.
* Participation in another interventional study that influences the primary outcome in this study (gestational age at delivery).
* Participation in this trial in a previous pregnancy.
* Delivery planned at a non-participating site

Where this trial is running

Birmingham, Alabama and 13 other locations

• University of Alabama - Birmingham — Birmingham, Alabama, United States (Recruiting)
• Regents of the University of California San Francisco — San Francisco, California, United States (Recruiting)
• Northwestern University — Chicago, Illinois, United States (Recruiting)
• Columbia University — New York, New York, United States (Recruiting)
• University of North Carolina - Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
• Duke University — Durham, North Carolina, United States (Recruiting)
• Case Western Reserve University — Cleveland, Ohio, United States (Recruiting)
• Ohio State University — Columbus, Ohio, United States (Recruiting)
• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• Magee Women's Hospital of UPMC — Pittsburgh, Pennsylvania, United States (Recruiting)
• Brown University — Providence, Rhode Island, United States (Recruiting)
• Baylor College of Medicine — Houston, Texas, United States (Recruiting)
• University of Texas - Houston — Houston, Texas, United States (Recruiting)
• University of Utah Medical Center — Salt Lake City, Utah, United States (Recruiting)

Study contacts

• Principal investigator: Rebecca G Clifton, PhD — The George Washington University Biostatistics Center
• Study coordinator: Rebecca G Clifton, PhD

Conditions Preterm Delivery; Obstetrical Complications; Stillbirth; Maternal Morbidity; Neonatal Morbidity; Prevention