Pre-EclampsiaPhase 2ASPERINNCT03893630
Role of ASpirin in Placental and Maternal Endothelial Cell Regulation IN Pre-eclampsia
A Phase 2 study testing Acetylsalicylic Acid 81 mg and Acetylsalicylic Acid 162 mg in people with Pre-Eclampsia, run by John O'Brien, MD at 1 site in United States.
Trial summary
Endothelial dysfunction and defective placental vascularization are hypothesized to be significant causes of preeclampsia. In preeclampsia, due to vascular endothelial dysfunction, vasoconstriction and platelet activation can result in severe features which alter pregnancy outcomes. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Eclampsia
- What is being tested?
- Acetylsalicylic Acid 81 mg and Acetylsalicylic Acid 162 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2019to 28 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- No risk factors for preeclampsia
- History of preterm preeclampsia
- Chronic hypertension
- Type 1 and Type 2 diabetes
- Renal diseases
- Autoimmune disease
Who cannot join
- Pregnant women younger than 18 years or older than 45 years
- Multiple gestations
- History of allergy (urticaria or anaphylaxis) to aspirin or aspirin-related products asthma that worsens after aspirin use
- Patients with gastrointestinal or genitourinary bleeding
- Patients with peptic ulcer disease
- Patients with severe liver dysfunction
Show all 9Show fewer
- Patients who have undergone bypass surgery
- Patients on anticoagulant medication(s)
- Women with anomalous fetus
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia
Endothelial dysfunction and defective placental vascularization are hypothesized to be significant causes of preeclampsia. In preeclampsia, due to vascular endothelial dysfunction, vasoconstriction and platelet activation can result in severe features which alter pregnancy outcomes. However, studies have shown that acetylsalicylic acid (Aspirin) can decrease endothelial dysfunction leading to decreased platelet aggregation which reduces adverse outcomes. The objective of our study is to determine if Aspirin has a dose-dependent response for modifying biomarkers reflective of maternal endothelial dysfunction when indicated for preeclampsia prevention in a cohort of women identified at risk for developing preeclampsia.
Pregnant women who are at risk for preeclampsia will be randomized to receive either 81mg Aspirin or 162mg Aspirin daily starting from 11-16 weeks of gestation until 36 weeks of gestation. A third, control group of women at low risk for preeclampsia will not receive aspirin. All women will be assessed with uterine artery Doppler studies and mean arterial blood pressures at three time points during pregnancy. Blood, urine, and cord blood samples will also be collected.
Read the detailed description
Eligible women will be identified in the late first or early second trimesters. Once recruited, women will be randomly assigned to either 81 mg or 162 mg per day dosing schedules. The randomization scheme will vary based on the body mass index (BMI) with separate schemes for women <=30 kg/m2 versus >30 kg/m2. Ultrasonographic assessment of biophysical biomarkers will be obtained at 11-16 weeks, 18-22 weeks, and 28-32 weeks gestation. Biologic samples of serum and urine will be obtained at the 11-16 week and 28-32 week visit. Upon delivery, cord blood and a placental specimen will also be obtained. Medication treatment will continue until 36 weeks gestation. Pregnancy and neonatal outcome data will be recorded.
- Conditions
- Pre-Eclampsia
- Being tested
- Acetylsalicylic Acid 81 mg, Acetylsalicylic Acid 162 mg, Control
- Keywords
- aspirin, pulsatility index, doppler, uterine, acetylsalicylic acid, preeclampsia, blood pressure
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetylsalicylic Acid 81 mgDrug
Also called Aspirin
Patients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.
Acetylsalicylic Acid 162 mgDrug
Also called Aspirin
Patients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.
ControlOther
Standard of Care
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | Patients will receive standard of care. Receives: Other: Control |
| Acetylsalicylic Acid 81mg | Experimental | Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin). Receives: Drug: Acetylsalicylic Acid 81 mg |
| Acetylsalicylic Acid 162mg | Experimental | Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin). Receives: Drug: Acetylsalicylic Acid 162 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulsatility Index (PI)
Uterine artery doppler is used to assess impedance to flow in the uterine artery three times: 11-16 weeks gestation(baseline), 18-22 weeks gestation (event 2), 28-32 weeks gestation (event 3). Data reported as change between 11-16 weeks gestation (baseline) and either 18-22 weeks gestation (event 2) or 28-32 weeks gestation (event 3).
difference in uterine artery pulsatility index (PI) is calculated as the difference in PI for each patient between each trimester visit. PI at each visit will be calculated by averaging left-side and right-side PIs from each of three (or all available) images on each side for each patient using ultrasound technology. Unit of measure is a ratio: difference between the peak systolic and end-diastolic velocities divided by the mean flow velocity Relative change in uterine artery pulsatility index is a measure of flow to the uterus. A greater difference from the baseline value represents a greater improvement in placental perfusion.
Measured: Three times between 11 and 32 weeks of gestation.
Secondary outcomes (9)
Onset of Pre-eclampsia
Frequency of Disease during pregnancy and postpartum as defined by American College of Obstetrics and Gynecology (ACOG) criteria
Measured: From enrollment at 11 weeks throughout pregnancy and postpartum ( 6 weeks after delivery), approximately 35 weeks
Severity of Pre-eclampsia
Frequency women are identified with Severe Features of the disease
Measured: From enrollment at 11 weeks throughout pregnancy and immediate postpartum ( 6 weeks after delivery), approximately 35 weeks
Composite Neonatal Outcomes Including Frequency of Intraventricular Hemorrhage (IVH), Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome (RDS), Necrotising Enterocolitis(NEC)
Frequency of adverse neonatal outcomes
Measured: Neonatal period ( first 28 days after birth)
Change in s-ICAM Levels Over Time
Serial biologic samples will be obtained in the first (baseline), second (event 2), and third (event 3) trimesters to measure changes in soluble Intercellular Adhesion Molecule (s-ICAM) levels over time.
Measured: Three times between 11 and 32 weeks of gestation
Change in PIGF Levels Over Time
Serial biologic samples will be obtained in the first (baseline), second (event 2), and third (event 3) trimesters to measure changes in placental growth factor (PIGF) levels over time.
Measured: Three times between 11 and 32 weeks of gestation
Change in CRP Levels Over Time
Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in C-reactive protein (CRP) levels over time.
Measured: Three times between 11 and 32 weeks of gestation
Change in IL-6 Over Time
Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in interleukin 6 (IL-6) levels over time.
Measured: Three times between 11 and 32 weeks of gestation
Change in TNF Over Time
Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in tumor necrosis factor (TNFα) levels over time.
Measured: Three times between 11 and 32 weeks of gestation
Gestational Age at Delivery
measured in weeks, from the first day of the last menstrual cycle to delivery
Measured: At Delivery, up to 41 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2019
- Study start25 Apr 2019
- Primary completion26 Jul 2022
- Study completion28 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- John O'Brien, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John O'Brien, MD, University of Kentucky
- Investigators
- John M O'Brien, MD, Principal investigator, University of KentuckyKatherine Vignes, MD, Study chair, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03893630
- Sponsor's protocol ID
- 47841
- Acronym
- ASPERIN
- Status last verified
- Aug 2025
- First submitted
- 1 Mar 2019
- Last updated
- 29 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.
PubMed 28657417Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007 May 26;369(9575):1791-1798. doi: 10.1016/S0140-6736(07)60712-0.
PubMed 17512048Roberge S, Bujold E, Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2018 Mar;218(3):287-293.e1. doi: 10.1016/j.ajog.2017.11.561. Epub 2017 Nov 11.
PubMed 29138036
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia
- ClinicalTrials.gov ID
- NCT03893630
- Acronym / sponsor ID
- ASPERIN / 47841
- Conditions
- Pre-Eclampsia
- Keywords
- aspirin, pulsatility index, doppler, uterine, acetylsalicylic acid, preeclampsia, blood pressure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- John O'Brien, MDUniversity, hospital or other
- Study start
- 25 Apr 2019 (actual)
- Primary completion
- 26 Jul 2022 (actual)
- Study completion
- 28 Sep 2022 (actual)
- First posted
- 28 Mar 2019 (actual)
- Results
- Posted 29 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Endothelial dysfunction and defective placental vascularization are hypothesized to be significant causes of preeclampsia. In preeclampsia, due to vascular endothelial dysfunction, vasoconstriction and platelet activation can result in severe features which alter pregnancy outcomes. However, studies have shown that acetylsalicylic acid (Aspirin) can decrease endothelial dysfunction leading to decreased platelet aggregation which reduces adverse outcomes. The objective of our study is to determine if Aspirin has a dose-dependent response for modifying biomarkers reflective of maternal endothelial dysfunction when indicated for preeclampsia prevention in a cohort of women identified at risk for developing preeclampsia.
Pregnant women who are at risk for preeclampsia will be randomized to receive either 81mg Aspirin or 162mg Aspirin daily starting from 11-16 weeks of gestation until 36 weeks of gestation. A third, control group of women at low risk for preeclampsia will not receive aspirin. All women will be assessed with uterine artery Doppler studies and mean arterial blood pressures at three time points during pregnancy. Blood, urine, and cord blood samples will also be collected.
Detailed description
Eligible women will be identified in the late first or early second trimesters. Once recruited, women will be randomly assigned to either 81 mg or 162 mg per day dosing schedules. The randomization scheme will vary based on the body mass index (BMI) with separate schemes for women <=30 kg/m2 versus >30 kg/m2. Ultrasonographic assessment of biophysical biomarkers will be obtained at 11-16 weeks, 18-22 weeks, and 28-32 weeks gestation. Biologic samples of serum and urine will be obtained at the 11-16 week and 28-32 week visit. Upon delivery, cord blood and a placental specimen will also be obtained. Medication treatment will continue until 36 weeks gestation. Pregnancy and neonatal outcome data will be recorded.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Other: ControlPatients will receive standard of care. |
| Acetylsalicylic Acid 81mg | Experimental | Drug: Acetylsalicylic Acid 81 mgPatients will receive low dose (81mg) acetylsalicylic acid (Aspirin). |
| Acetylsalicylic Acid 162mg | Experimental | Drug: Acetylsalicylic Acid 162 mgPatients will receive low dose (162mg) acetylsalicylic acid (Aspirin). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- No risk factors for preeclampsia
- History of preterm preeclampsia
- Chronic hypertension
- Type 1 and Type 2 diabetes
- Renal diseases
Key exclusion criteria (9 listed)
- Pregnant women younger than 18 years or older than 45 years
- Multiple gestations
- History of allergy (urticaria or anaphylaxis) to aspirin or aspirin-related products asthma that worsens after aspirin use
- Patients with gastrointestinal or genitourinary bleeding
- Patients with peptic ulcer disease
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 |
|---|---|---|
| Acetylsalicylic Acid 81 mgAlso: AspirinPatients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation. | Drug | Acetylsalicylic Acid 81mg |
| Acetylsalicylic Acid 162 mgAlso: AspirinPatients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation. | Drug | Acetylsalicylic Acid 162mg |
| ControlStandard of Care | Other | Control Group |
Primary outcome
Change in Pulsatility Index (PI)
Time frame: Three times between 11 and 32 weeks of gestation.
Uterine artery doppler is used to assess impedance to flow in the uterine artery three times: 11-16 weeks gestation(baseline), 18-22 weeks gestation (event 2), 28-32 weeks gestation (event 3). Data reported as change between 11-16 weeks gestation (baseline) and either 18-22 weeks gestation (event 2) or 28-32 weeks gestation (event 3). difference in uterine artery pulsatility index (PI) is calculated as the difference in PI for each patient between each trimester visit. PI at each visit will be calculated by averaging left-side and right-side PIs from each of three (or all available) images on each side for each patient using ultrasound technology. Unit of measure is a ratio: difference between the peak systolic and end-diastolic velocities divided by the mean flow velocity Relative change in uterine artery pulsatility index is a measure of flow to the uterus. A greater difference from the baseline value represents a greater improvement in placental perfusion.
9 secondary outcomes
Onset of Pre-eclampsia
Time frame: From enrollment at 11 weeks throughout pregnancy and postpartum ( 6 weeks after delivery), approximately 35 weeks
Severity of Pre-eclampsia
Time frame: From enrollment at 11 weeks throughout pregnancy and immediate postpartum ( 6 weeks after delivery), approximately 35 weeks
Composite Neonatal Outcomes Including Frequency of Intraventricular Hemorrhage (IVH), Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome (RDS), Necrotising Enterocolitis(NEC)
Time frame: Neonatal period ( first 28 days after birth)
Change in s-ICAM Levels Over Time
Time frame: Three times between 11 and 32 weeks of gestation
Change in PIGF Levels Over Time
Time frame: Three times between 11 and 32 weeks of gestation
Change in CRP Levels Over Time
Time frame: Three times between 11 and 32 weeks of gestation
Change in IL-6 Over Time
Time frame: Three times between 11 and 32 weeks of gestation
Change in TNF Over Time
Time frame: Three times between 11 and 32 weeks of gestation
Gestational Age at Delivery
Time frame: At Delivery, up to 41 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28657417Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.
- Background: PubMed 17512048Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007 May 26;369(9575):1791-1798. doi: 10.1016/S0140-6736(07)60712-0.
- Background: PubMed 29138036Roberge S, Bujold E, Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2018 Mar;218(3):287-293.e1. doi: 10.1016/j.ajog.2017.11.561. Epub 2017 Nov 11.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
John M O'Brien, MD principal investigator
University of Kentucky
Katherine Vignes, MD study chair
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetylsalicylic Acid 81 mg and Acetylsalicylic Acid 162 mg in people with Pre-Eclampsia, run by John O'Brien, MD 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 6 inclusion and 9 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: finished, as of the sponsor's last update on 29 Aug 2025. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulsatility Index (PI) (time frame: Three times between 11 and 32 weeks of gestation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03893630, which also lists 3 linked publications.
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 29 Aug 2025.