Preeclampsia
Conditions
Keywords
preeclampsia, Aspirin
Brief summary
This is a randomized controlled trial to estimate the efficacy of low dose aspirin for preventing preeclampsia in women identified as high risk. The investigators hypothesize that the risk of preeclampsia in women identified by a first trimester multiparameter predictive model to be at high risk will be significantly reduced by initiating low dose aspirin early in pregnancy.
Detailed description
This will be a randomized control trial to estimate the efficacy of low dose aspirin in preventing preeclampsia in women identified in the first trimester to be at high risk. We will also obtain maternal blood, cord blood and placenta specimen for basic science studies to attempt to dissect biological mechanisms of aspirin effects. In addition we will conduct a cost-benefit analysis to determine the cost effectiveness of screening and using aspirin prophylaxis for screen positive women. Rationale for Design: The randomized control trial is the 'gold standard' of research design. Other designs such as case-control, retrospective cohort and prospective cohort are limited by potential bias and confounding. Randomly assigning subjects to different interventions minimizes selection bias. The random assignment also results in groups that are likely to be similar with regards to important confounding variables. This minimizes confounding by both measured and unmeasured factors. While random allocation does not guarantee the groups will be identical, it does ensure that any differences between them are due to chance alone. Finally, randomization produces groups that are random samples of the population. This permits use of standard statistical tests that are based on probability theory.
Interventions
DRUGAspirin
DRUGplacebo
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
* Singleton pregnancy undergoing ultrasound examination at 9 0/7 - 14 6/7 weeks * any one or more factors identified as high risk from the identified risk factors: Chronic hypertension, prepregnancy diabetes mellitus, previous preeclampsia, obesity (BMI \>30), bilateral uterine artery notches preeclampsia risk score greater than 6, low PAPP-A ( \< 0.52 MoM)
Exclusion criteria
* Multiple gestations, * fetal aneuploidy * major fetal structural anomaly * bleeding disorder * allergy to aspirin * women already on aspirin or heparin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Preeclampsia | within 3 months prior to delivery | Preeclampsia diagnosed per ACOG criteria: Blood pressure greater than 140/90 on 2 occasions 6 hrs apart and significant proteinuria (greater than 300mg in 24hrs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | within 3 months of delivery | Intrauterine growth restriction (IUGR) - estimated fetal weight less than 10th percentile early preeclampsia - preeclampsia delivered prior to 34 weeks severe preeclampsia - blood pressure greater then 160/110 gestational hypertension - hypertension without features of preeclampsia preterm birth, stillbirth, placental abruption, antepartum hemorrhage, neonatal death, NICU admission, miscarriage. Statistical significance not reported due to the low recruitment and poor patient compliance. |
Countries
United States
Participant flow
Pre-assignment details
Of 1470 women screened, 138 were screen positive, and 53 consented to participate in the study and were randomized. Ten women in the aspirin group and 13 in the placebo group dropped out of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 1 capsule orally daily | 14 |
| Aspirin 81mg, 1 capsule orally daily | 16 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | termination of pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 7 |
Baseline characteristics
| Characteristic | Placebo | Aspirin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 16 Participants | 30 Participants |
| Age, Continuous | 31.6 years STANDARD_DEVIATION 6.1 | 30.0 years STANDARD_DEVIATION 5 | 30.8 years STANDARD_DEVIATION 5.5 |
| Race/Ethnicity, Customized Black | 11 Participants | 4 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 11 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Sex Female | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Sex Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 3 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Number of Participants With Preeclampsia
Preeclampsia diagnosed per ACOG criteria: Blood pressure greater than 140/90 on 2 occasions 6 hrs apart and significant proteinuria (greater than 300mg in 24hrs).
Time frame: within 3 months prior to delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Preeclampsia | 3 Participants |
| Aspirin | Number of Participants With Preeclampsia | 3 Participants |
Secondary
Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage
Intrauterine growth restriction (IUGR) - estimated fetal weight less than 10th percentile early preeclampsia - preeclampsia delivered prior to 34 weeks severe preeclampsia - blood pressure greater then 160/110 gestational hypertension - hypertension without features of preeclampsia preterm birth, stillbirth, placental abruption, antepartum hemorrhage, neonatal death, NICU admission, miscarriage. Statistical significance not reported due to the low recruitment and poor patient compliance.
Time frame: within 3 months of delivery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | miscarriage | 1 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Small for gestational age (IUGR) | 1 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Gestational hypertension | 0 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Early preeclampsia | 1 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Severe preeclampsia | 3 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Preterm birth | 2 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Stillbirth | 0 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Placental abruption | 0 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | antepartum hemorrhage | 0 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | neonatal death | 0 participants |
| Placebo | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | NICU admission | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | NICU admission | 2 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Stillbirth | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Small for gestational age (IUGR) | 1 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | neonatal death | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Gestational hypertension | 2 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Placental abruption | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Early preeclampsia | 1 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | miscarriage | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Severe preeclampsia | 3 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | antepartum hemorrhage | 0 participants |
| Aspirin | Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage | Preterm birth | 1 participants |