Clinical trial NCT06408181: APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia
Official title: APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pre-Eclampsia
Pregnancy Loss
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2024-05-10
Enrollment: 1150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to investigate the effects of early initiation of double low-dose aspirin in pregnant women. The main questions it aims to answer are:

Does this dose and timing of aspirin reduce the risk of pre-eclampsia compared to standard recommendations? Does this dose and timing of aspirin reduce the risk of pregnancy loss compared to standard recommendations? Participants will begin taking at no later than 6 weeks 6 days gestational age, either 162mg of aspirin through delivery or placebo until 12 weeks and then 81mg of aspirin through delivery.


Eligibility criteria: Inclusion Criteria

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Ability to take oral medication and be willing to adhere to the prescribed aspirin regimen.
4. Patients with a gestation less than or equal to 6 weeks, 6 days (as determined by patient record of LMP or ART date).
5. Patients between 18-45-year old who have one or more risk factors for preeclampsia and/or pregnancy loss, including:

   1. preeclampsia in a previous pregnancy,
   2. gestational diabetes in a previous pregnancy,
   3. any documentation of fetal growth restriction or low birth weight in a prior pregnancy,
   4. preterm birth in a previous pregnancy,
   5. known multifetal gestation at enrollment,
   6. chronic hypertension,
   7. pregestational diabetes,
   8. kidney disease,
   9. systemic lupus erythematosus,
   10. nulliparity,
   11. pre-pregnancy body mass index \>30,
   12. family history of preeclampsia (i.e., mother or sister),
   13. Black persons (due to social, not biological reasons),
   14. Maternal age 35 years or older,
   15. lower income (will be determined by qualification of public health insurance),
   16. conceived with fertility treatment (including in vitro fertilization, ovulation induction, or intrauterine insemination),
   17. history of one or more prior pregnancy losses \<20 weeks gestation,
   18. history of stillbirth in a prior pregnancy,
   19. An interval of greater than 10 years since the last pregnancy.

Exclusion Criteria

1. Known allergies to aspirin or non-steroidal anti-inflammatory agents (NSAID);
2. Clinical indication for anticoagulant therapy, including prior or current thrombosis, antiphospholipid syndrome, or known major thrombophilia;
3. Clinical indication for chronic use of NSAIDS during pregnancy;
4. Medical contraindication to aspirin therapy, including untreated uncontrolled asthma, untreated symptomatic nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
5. Patients with pelvic pain or bleeding who require urgent care (i.e., active vaginal bleeding greater than or equal to expected menses, open cervical os suggesting active miscarriage or severe pain requiring evaluation for ectopic pregnancy)

Primary outcomes:
measure: Preeclampsia with or without severe features
timeFrame: from 20 weeks pregnancy to delivery, approximately 20 weeks
measure: Pregnancy Loss
timeFrame: from enrollment to time of pregnancy loss, up to 24 weeks gestation
Secondary outcomes:
measure: Composite outcome of hypertensive disorders of pregnancy or pregnancy loss
timeFrame: From enrollment to end of pregnancy, up to 38 weeks
measure: Preterm preeclampsia
timeFrame: From enrollment up to 37 weeks of pregnancy, up to 37 weeks of pregnancy
measure: Term preeclampsia
timeFrame: From 37 weeks until delivery, up to 3 weeks
measure: Gestational Hypertension
timeFrame: From 20 weeks of pregnancy to delivery, approximately 20 weeks
measure: Preeclampsia with severe features
timeFrame: From 20 weeks of pregnancy to delivery, up to 20 weeks
measure: Preeclampsia without severe features
timeFrame: From 20 weeks of pregnancy to delivery, up to 20 weeks
measure: Biochemical pregnancy loss
timeFrame: From enrollment to time of pregnancy loss, up to approximately 20 weeks
measure: Clinical pregnancy loss
timeFrame: From time of first ultrasound to 20 weeks pregnancy
measure: Preterm birth
timeFrame: From enrollment to 36 weeks 6 days of pregnancy, up to delivery
measure: Small for gestational age
timeFrame: At time of delivery
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Enrique Schisterman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Kurt Barnhart, MD
role: PRINCIPAL_INVESTIGATOR
References: