APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia

University of Pennsylvania

Status and phase: Enrolling; Phase 3

Conditions: Pre-Eclampsia; Pregnancy Loss

Treatments: Drug: Aspirin 162 mg; Drug: Aspirin 81mg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06408181

1R01HD112308-01 (U.S. NIH Grant/Contract)

854886

Details and patient eligibility

About

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.

Enrollment: 1,150 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,150 participants in 2 patient groups, including a placebo group

Double low-dose aspirin

Active Comparator group

Description:

Participants will take 2 81mg aspirin tablets daily from entrance into the trial until delivery.

Treatment:

Drug: Aspirin 162 mg

Standard of Care

Placebo Comparator group

Description:

Participants will take 2 placebo pills from entrance into the study until 12 weeks gestational age, they will then take 1 placebo pill and 1 81mg aspirin until delivery.

Treatment:

Drug: Aspirin 81mg