Aspirin Dose Escalation for the Prevention of Recurrent Preterm Delivery Trial

Open to females ages 14 years and up

• 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.

• 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