Role of ASpirin in Placental and Maternal Endothelial Cell Regulation IN Pre-eclampsia

Role of Aspirin in Maternal Endothelial Dysfunction and Uterine Artery Blood Flow in Women at Risk for Preeclampsia

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03893630

Acronym

ASPERIN

Enrollment

208

Registered

2019-03-28

Start date

2019-04-25

Completion date

2022-09-28

Last updated

2025-08-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pre-Eclampsia

Keywords

aspirin, pulsatility index, doppler, uterine, acetylsalicylic acid, preeclampsia, blood pressure

Brief 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. 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.

Interventions

DRUGAcetylsalicylic Acid 81 mg

Patients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.

DRUGAcetylsalicylic Acid 162 mg

Patients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.

OTHERControl

Standard of Care

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

(control) • No risk factors for preeclampsia Inclusion Criteria (pre-eclampsia) * History of preterm preeclampsia * Chronic hypertension * Type 1 and Type 2 diabetes * Renal diseases * Autoimmune disease

Exclusion criteria

* 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 * Patients who have undergone bypass surgery * Patients on anticoagulant medication(s) * Women with anomalous fetus

Design outcomes

Primary

Measure	Time frame	Description
Change in Pulsatility Index (PI)	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.

Secondary

Measure	Time frame	Description
Severity of Pre-eclampsia	From enrollment at 11 weeks throughout pregnancy and immediate postpartum ( 6 weeks after delivery), approximately 35 weeks	Frequency women are identified with Severe Features of the disease
Composite Neonatal Outcomes Including Frequency of Intraventricular Hemorrhage (IVH), Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome (RDS), Necrotising Enterocolitis(NEC)	Neonatal period ( first 28 days after birth)	Frequency of adverse neonatal outcomes
Change in s-ICAM Levels Over Time	Three times between 11 and 32 weeks of gestation	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.
Change in PIGF Levels Over Time	Three times between 11 and 32 weeks of gestation	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.
Onset of Pre-eclampsia	From enrollment at 11 weeks throughout pregnancy and postpartum ( 6 weeks after delivery), approximately 35 weeks	Frequency of Disease during pregnancy and postpartum as defined by American College of Obstetrics and Gynecology (ACOG) criteria
Change in IL-6 Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in interleukin 6 (IL-6) levels over time.
Change in TNF Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in tumor necrosis factor (TNFα) levels over time.
Gestational Age at Delivery	At Delivery, up to 41 weeks	measured in weeks, from the first day of the last menstrual cycle to delivery
Change in CRP Levels Over Time	Three times between 11 and 32 weeks of gestation	Serial biologic samples will be obtained in the first, second, and third trimesters to measure changes in C-reactive protein (CRP) levels over time.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Control Group Patients will receive standard of care. Control: Standard of Care	65
Acetylsalicylic Acid 81mg Patients will receive low dose (81mg) acetylsalicylic acid (Aspirin). Acetylsalicylic Acid 81 mg: Patients will receive 81mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.	68
Acetylsalicylic Acid 162mg Patients will receive low dose (162mg) acetylsalicylic acid (Aspirin). Acetylsalicylic Acid 162 mg: Patients will receive 162mg acetylsalicylic acid daily, initiated between 11 and 16 weeks of gestation and continued until 36 weeks of gestation.	75
Total	208

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Discontinued Intervention	0	4	2
Overall Study	Lost to Follow-up	5	4	2
Overall Study	Withdrawal by Subject	3	6	3

Baseline characteristics

Characteristic	Control Group	Acetylsalicylic Acid 81mg	Acetylsalicylic Acid 162mg	Total
Age, Continuous	29.5 years STANDARD_DEVIATION 6.3	29.6 years STANDARD_DEVIATION 5.9	29.8 years STANDARD_DEVIATION 6.1	29.7 years STANDARD_DEVIATION 6
BMI at enrollment	29.2 kg/m2 STANDARD_DEVIATION 7.9	35.7 kg/m2 STANDARD_DEVIATION 10	34.1 kg/m2 STANDARD_DEVIATION 8.5	33.1 kg/m2 STANDARD_DEVIATION 9.2
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	9 Participants	9 Participants	26 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants	59 Participants	66 Participants	182 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Method of Conception Assisted by Ovulation Drugs	3 Participants	3 Participants	2 Participants	8 Participants
Method of Conception In Vitro Fertilization	2 Participants	1 Participants	2 Participants	5 Participants
Method of Conception Natural	60 Participants	64 Participants	71 Participants	195 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Asian	1 Participants	2 Participants	2 Participants	5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants	9 Participants	14 Participants	29 Participants
Race/Ethnicity, Customized Hispanic	8 Participants	3 Participants	9 Participants	20 Participants
Race/Ethnicity, Customized More than one race	0 Participants	2 Participants	3 Participants	5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized White	49 Participants	52 Participants	45 Participants	146 Participants
Region of Enrollment United States	65 participants	68 participants	75 participants	208 participants
Sex: Female, Male Female	65 Participants	68 Participants	75 Participants	208 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 65	0 / 68	0 / 75
other Total, other adverse events	3 / 65	3 / 68	2 / 75
serious Total, serious adverse events	8 / 65	12 / 68	15 / 75

Outcome results

Primary

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.

Time frame: Three times between 11 and 32 weeks of gestation.

Population: Participants delivered or lost to follow up not included

Arm	Measure	Group	Value (MEAN)	Dispersion
Control Group	Change in Pulsatility Index (PI)	Baseline to Event 2	-0.56 ratio	Standard Deviation 0.55
Control Group	Change in Pulsatility Index (PI)	Baseline to Event 3	-0.88 ratio	Standard Deviation 0.56
Acetylsalicylic Acid 81mg	Change in Pulsatility Index (PI)	Baseline to Event 2	-0.53 ratio	Standard Deviation 0.34
Acetylsalicylic Acid 81mg	Change in Pulsatility Index (PI)	Baseline to Event 3	-0.72 ratio	Standard Deviation 0.41
Acetylsalicylic Acid 162mg	Change in Pulsatility Index (PI)	Baseline to Event 2	-0.43 ratio	Standard Deviation 0.34
Acetylsalicylic Acid 162mg	Change in Pulsatility Index (PI)	Baseline to Event 3	-0.58 ratio	Standard Deviation 0.54

Secondary

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.