Pre-EclampsiaPhase 3APPLENCT06408181
APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia
A Phase 3 study testing Aspirin 162 mg and Aspirin 81mg in people with Pre-Eclampsia and Pregnancy Loss, run by University of Pennsylvania at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Pre-Eclampsia, Pregnancy Loss
- What is being tested?
- Aspirin 162 mg and Aspirin 81mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,150 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2024to Jun 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- Known allergies to aspirin. Exclusion to allergies to other non-steroidal anti-inflammatory agents (NSAID) will be determined on a case-by-case basis;
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Enrique Schisterman, PhD contact
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Theresa Delahanty, theresa.delahanty@pennmedicine.upenn.edu
Andrea Morley, andrea.morley@pennmedicine.upenn.edu
About this study
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
- Being tested
- Aspirin 162 mg, Aspirin 81mg
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin 162 mgDrug
Also called acetylsalicylic acid, ASA
Aspirin is a nonsteroidal anti-inflammatory drug.
Aspirin 81mgDrug
Also called acetylsalicylic acid, ASA
Aspirin is a nonsteroidal anti-inflammatory drug.
| Study group | Role | What they receive |
|---|---|---|
| Double low-dose aspirin | Active comparator | Participants will take 2 81mg aspirin tablets daily from entrance into the trial until delivery. Receives: 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. Receives: Drug: Aspirin 81mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preeclampsia with or without severe features
defined as two blood pressures (BPs) ≥ 140/90 mmHg at least 4 hours apart with proteinuria
Measured: from 20 weeks pregnancy to delivery, approximately 20 weeks
Pregnancy Loss
Pregnancy loss prior to 24 weeks gestation
Measured: 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
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
Measured: From enrollment to end of pregnancy, up to 38 weeks
Preterm preeclampsia
Diagnosis of preterm preeclampsia, occurring prior to 37 weeks in pregnancy
Measured: From enrollment up to 37 weeks of pregnancy, up to 37 weeks of pregnancy
Term preeclampsia
Diagnosis of term preeclampsia, occurring at 37 weeks or later in pregnancy
Measured: From 37 weeks until delivery, up to 3 weeks
Gestational Hypertension
Defined as two BPs ≥ 140/90 mmHg at least 4 hours apart without proteinuria
Measured: From 20 weeks of pregnancy to delivery, approximately 20 weeks
Preeclampsia with severe features
Diagnosis of preeclampsia with severe hypertension and/or specific signs or symptoms of significant end-organ dysfunction
Measured: From 20 weeks of pregnancy to delivery, up to 20 weeks
Preeclampsia without severe features
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.
Measured: From 20 weeks of pregnancy to delivery, up to 20 weeks
Biochemical pregnancy loss
Defined as losses that occur prior to identification of a gestational sac via ultrasound
Measured: From enrollment to time of pregnancy loss, up to approximately 20 weeks
Clinical pregnancy loss
Defined as any pregnancy loss occurring following ultrasound confirmation of pregnancy
Measured: From time of first ultrasound to 20 weeks pregnancy
Preterm birth
Defined as delivery at less than 37 weeks gestation
Measured: From enrollment to 36 weeks 6 days of pregnancy, up to delivery
Small for gestational age
Defined as a birth weight less than 10th percentile for gestational age
Measured: At time of delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2024
- Study start12 Jun 2024
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Enrique Schisterman, PhD, Principal investigator, University of PennsylvaniaKurt Barnhart, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06408181
- Sponsor's protocol ID
- 854886
- Other IDs
- 1R01HD112308-01
- Acronym
- APPLE
- Status last verified
- Sep 2026
- First submitted
- 1 May 2024
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- APPLE: Aspirin to Prevent Pregnancy Loss and Preeclampsia
- ClinicalTrials.gov ID
- NCT06408181
- Acronym / sponsor ID
- APPLE / 854886
- Conditions
- Pre-Eclampsia, Pregnancy Loss
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,150 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 12 Jun 2024 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 10 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double low-dose aspirin | Active comparator | Drug: Aspirin 162 mgParticipants will take 2 81mg aspirin tablets daily from entrance into the trial until delivery. |
| Standard of Care | Placebo comparator | Drug: Aspirin 81mgParticipants 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (24 listed)
- 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:
Key exclusion criteria (5 listed)
- Known allergies to aspirin. Exclusion to allergies to other non-steroidal anti-inflammatory agents (NSAID) will be determined on a case-by-case basis;
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin 162 mgAlso: acetylsalicylic acid, ASAAspirin is a nonsteroidal anti-inflammatory drug. | Drug | Double low-dose aspirin |
| Aspirin 81mgAlso: acetylsalicylic acid, ASAAspirin is a nonsteroidal anti-inflammatory drug. | Drug | Standard of Care |
Primary outcome
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
Pregnancy Loss
Time frame: from enrollment to time of pregnancy loss, up to 24 weeks gestation
Pregnancy loss prior to 24 weeks gestation
10 secondary outcomes
Composite outcome of hypertensive disorders of pregnancy or pregnancy loss
Time frame: From enrollment to end of pregnancy, up to 38 weeks
Preterm preeclampsia
Time frame: From enrollment up to 37 weeks of pregnancy, up to 37 weeks of pregnancy
Term preeclampsia
Time frame: From 37 weeks until delivery, up to 3 weeks
Gestational Hypertension
Time frame: From 20 weeks of pregnancy to delivery, approximately 20 weeks
Preeclampsia with severe features
Time frame: From 20 weeks of pregnancy to delivery, up to 20 weeks
Preeclampsia without severe features
Time frame: From 20 weeks of pregnancy to delivery, up to 20 weeks
Biochemical pregnancy loss
Time frame: From enrollment to time of pregnancy loss, up to approximately 20 weeks
Clinical pregnancy loss
Time frame: From time of first ultrasound to 20 weeks pregnancy
Preterm birth
Time frame: From enrollment to 36 weeks 6 days of pregnancy, up to delivery
Small for gestational age
Time frame: At time of delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Enrique Schisterman, PhD contact
Enrique Schisterman, PhD principal investigator
University of Pennsylvania
Kurt Barnhart, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aspirin 162 mg and Aspirin 81mg in people with Pre-Eclampsia and Pregnancy Loss, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kurt T Barnhart, MD (215-662-2974, kbarnhart@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preeclampsia with or without severe features (time frame: from 20 weeks pregnancy to delivery, approximately 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.