APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia

NCT06408181 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 8548861R01HD112308-01
• Study Type: interventional
• Target: 1,150
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Preeclampsia with or without severe features

  defined as two blood pressures (BPs) ≥ 140/90 mmHg at least 4 hours apart with proteinuria

  from 20 weeks pregnancy to delivery, approximately 20 weeks

• Pregnancy Loss

  Pregnancy loss prior to 24 weeks gestation

  from enrollment to time of pregnancy loss, up to 24 weeks gestation

Secondary Outcomes (10)

• Composite outcome of hypertensive disorders of pregnancy or pregnancy loss

  From enrollment to end of pregnancy, up to 38 weeks

• Preterm preeclampsia

  From enrollment up to 37 weeks of pregnancy, up to 37 weeks of pregnancy

• Term preeclampsia

  From 37 weeks until delivery, up to 3 weeks

• Gestational Hypertension

  From 20 weeks of pregnancy to delivery, approximately 20 weeks

• Preeclampsia with severe features

  From 20 weeks of pregnancy to delivery, up to 20 weeks

Study Arms (2)

Double low-dose aspirin

ACTIVE COMPARATOR

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

Drug: Aspirin 162 mg

Standard of Care

PLACEBO COMPARATOR

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.

Drug: Aspirin 81mg

Interventions

Aspirin 162 mg DRUG

Aspirin is a nonsteroidal anti-inflammatory drug.

Also known as: acetylsalicylic acid, ASA

Double low-dose aspirin

Aspirin 81mg DRUG

Aspirin is a nonsteroidal anti-inflammatory drug.

Also known as: acetylsalicylic acid, ASA

Standard of Care

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability to take oral medication and be willing to adhere to the prescribed aspirin regimen.
• Patients with a gestation less than or equal to 6 weeks, 6 days (as determined by patient record of LMP or ART date).
• Patients between 18-45-year old who have one or more risk factors for preeclampsia and/or pregnancy loss, including:
• preeclampsia in a previous pregnancy,
• gestational diabetes in a previous pregnancy,
• any documentation of fetal growth restriction or low birth weight in a prior pregnancy,
• preterm birth in a previous pregnancy,
• known multifetal gestation at enrollment,
• chronic hypertension,
• pregestational diabetes,
• kidney disease,
• systemic lupus erythematosus,
• nulliparity,

You may not qualify if:

• Known allergies to aspirin or non-steroidal anti-inflammatory agents (NSAID);
• Clinical indication for anticoagulant therapy, including prior or current thrombosis, antiphospholipid syndrome, or known major thrombophilia;
• Clinical indication for chronic use of NSAIDS during pregnancy;
• Medical contraindication to aspirin therapy, including untreated uncontrolled asthma, untreated symptomatic nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
• 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)

Sponsors & Collaborators

• University of Pennsylvania: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Enrique Schisterman, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Kurt Barnhart, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kurt T Barnhart, MD

CONTACT

215-662-2974; kbarnhart@pennmedicine.upenn.edu

Enrique Schisterman, PhD

CONTACT

enrique.schisterman@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2024
• First Posted: May 10, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (1)