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Recruiting

NCT Number: NCT06408181

APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia

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.

Recruiting

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Key information

Age range

18 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location status: Recruiting

Location contact

Andrea Morley

CONTACT

[email protected]

Theresa Delahanty

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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,
  • pre-pregnancy body mass index >30,
  • family history of preeclampsia (i.e., mother or sister),
  • Black persons (due to social, not biological reasons),
  • Maternal age 35 years or older,
  • lower income (will be determined by qualification of public health insurance),
  • conceived with fertility treatment (including in vitro fertilization, ovulation induction, or intrauterine insemination),
  • history of one or more prior pregnancy losses <20 weeks gestation,
  • history of stillbirth in a prior pregnancy,
  • An interval of greater than 10 years since the last pregnancy.

Exclusion criteria

  • 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)

Treatment and study plan

Aspirin 162 mg

Drug

Aspirin is a nonsteroidal anti-inflammatory drug.

Other names: acetylsalicylic acid, ASA

Aspirin 81mg

Drug

Aspirin is a nonsteroidal anti-inflammatory drug.

Other names: acetylsalicylic acid, ASA

Primary outcomes

  1. Preeclampsia with or without severe features

    Time frame: from 20 weeks pregnancy to delivery, approximately 20 weeks

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

  2. Pregnancy Loss

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

    Pregnancy loss prior to 24 weeks gestation

Secondary outcomes

  1. Composite outcome of hypertensive disorders of pregnancy or pregnancy loss

    Time frame: From enrollment to end of pregnancy, up to 38 weeks

    This composite outcome will include the diagnosis of any of the following: preterm preeclampsia, term preeclampsia, gestational hypertension, preeclampsia with severe features, preeclampsia without severe features, biochemical pregnancy loss, clinical pregnancy loss

  2. Preterm preeclampsia

    Time frame: From enrollment up to 37 weeks of pregnancy, up to 37 weeks of pregnancy

    Diagnosis of preterm preeclampsia, occurring prior to 37 weeks in pregnancy

  3. Term preeclampsia

    Time frame: From 37 weeks until delivery, up to 3 weeks

    Diagnosis of term preeclampsia, occurring at 37 weeks or later in pregnancy

  4. Gestational Hypertension

    Time frame: From 20 weeks of pregnancy to delivery, approximately 20 weeks

    Defined as two BPs ≥ 140/90 mmHg at least 4 hours apart without proteinuria

  5. Preeclampsia with severe features

    Time frame: From 20 weeks of pregnancy to delivery, up to 20 weeks

    Diagnosis of preeclampsia with severe hypertension and/or specific signs or symptoms of significant end-organ dysfunction

  6. Preeclampsia without severe features

    Time frame: From 20 weeks of pregnancy to delivery, up to 20 weeks

    defined as two BPs ≥160/110 mmHg at least 4 hours apart or any of the following lab abnormalities or symptoms: platelets <100,000/microliter, liver enzymes at least twice the normal concentration, and/or severe right upper quadrant/epigastric pain, serum creatinine > 1.1 mg/dL or a doubling of baseline serum creatinine, pulmonary edema, or new-onset cerebral or visual disturbances (headache, blurry vision). Preeclampsia super-imposed on chronic hypertension will also be considered as part of this outcome.

  7. Biochemical pregnancy loss

    Time frame: From enrollment to time of pregnancy loss, up to approximately 20 weeks

    Defined as losses that occur prior to identification of a gestational sac via ultrasound

  8. Clinical pregnancy loss

    Time frame: From time of first ultrasound to 20 weeks pregnancy

    Defined as any pregnancy loss occurring following ultrasound confirmation of pregnancy

  9. Preterm birth

    Time frame: From enrollment to 36 weeks 6 days of pregnancy, up to delivery

    Defined as delivery at less than 37 weeks gestation

  10. Small for gestational age

    Time frame: At time of delivery

    Defined as a birth weight less than 10th percentile for gestational age

Study contacts

Contact information is provided by the study sponsor or research team.

Enrique Schisterman, PhD

CONTACT

[email protected]

Kurt T Barnhart, MD

CONTACT

[email protected]

215-662-2974

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

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

Registry information

Acronym: APPLE

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
May 10, 2024
Registry last updated
Jan 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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