APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia

NCT ID: NCT06408181

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-12
• Study Completion Date: 2029-06-30

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.

Conditions

Pre-Eclampsia; Pregnancy Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Double low-dose aspirin

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

Group Type: ACTIVE_COMPARATOR

Aspirin 162 mg

Intervention Type: DRUG

Aspirin is a nonsteroidal anti-inflammatory drug.

Standard of Care

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.

Group Type: PLACEBO_COMPARATOR

Aspirin 81mg

Intervention Type: DRUG

Aspirin is a nonsteroidal anti-inflammatory drug.

Interventions

Aspirin 162 mg

Aspirin is a nonsteroidal anti-inflammatory drug.

Intervention Type: DRUG

Aspirin 81mg

Aspirin is a nonsteroidal anti-inflammatory drug.

Intervention Type: DRUG

Other Intervention Names

acetylsalicylic acid; ASA; acetylsalicylic acid; ASA

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enrique Schisterman, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Kurt Barnhart, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kurt T Barnhart, MD

Role: CONTACT

kbarnhart@pennmedicine.upenn.edu

215-662-2974

Enrique Schisterman, PhD

Role: CONTACT

enrique.schisterman@pennmedicine.upenn.edu

Facility Contacts

Theresa Delahanty

Role: primary

theresa.delahanty@pennmedicine.upenn.edu

Andrea Morley

Role: backup

andrea.morley@pennmedicine.upenn.edu

Other Identifiers

1R01HD112308-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

854886

Identifier Type: -

Identifier Source: org_study_id