Preeclampsia Postpartum
Conditions
Keywords
Preeclampsia, Postpartum, Aspirin, sFlt-1
Brief summary
The purpose of this research study is to evaluate the effect of low-dose aspirin on recovery from severe preeclampsia (a high blood pressure disorder of pregnancy) among women who have given birth. We hypothesize that taking aspirin for the first week after giving birth will enhance recovery from preeclampsia by decreasing the levels of a protein called soluble fms-like tyrosine kinase (sFlt-1), which is thought to be a main contributor to the development of preeclampsia, and speeding up return to a normal blood pressure.
Detailed description
Preeclampsia is a condition of the antenatal and postpartum periods, which manifests as new-onset hypertension and end-organ damage. Globally, preeclampsia is estimated to affect up to 9% of all pregnancies, though as many as two-thirds of patients who receive this diagnosis will remain hypertensive beyond the time of their postpartum hospital discharge. Because of this, postpartum preeclampsia is the leading cause of postpartum hospital readmission in the United States. Anti-hypertensive medications and magnesium sulfate are temporizing therapies aimed at preventing the immediate sequelae of preeclampsia such as seizures, stroke, and end-organ damage. However, there are no therapies directly targeting the pathophysiology underlying postpartum preeclampsia, which poses difficulties in promoting blood pressure recovery to a normotensive state. Preeclampsia is considered a disorder of abnormal placentation, leading to the release of abnormal pro-angiogenic, anti-angiogenic, and vasoactive molecules. Specifically, excess elevations in anti-angiogenic proteins like soluble fms-like tyrosine kinase 1 (sFlt-1) relative to pro-angiogenic proteins like placental growth factor (PlGF) are thought to cause vasospasm and, in turn, hypertension. As such, it seems plausible that persistent postpartum sFlt-1 elevation is implicated in the pathophysiology of postpartum preeclampsia. At low doses, acetylsalicylic acid, or aspirin, has been proven to target the aforementioned angiogenic imbalance by decreasing serum sFlt-1 levels. While aspirin is widely used during pregnancy to mitigate the risk of preeclampsia, the utility of aspirin in the postpartum period to target these pathways and promote BP recovery to a normotensive state is unknown. The central hypothesis of this trial is that use of aspirin in the first week postpartum will enhance recovery from preeclampsia by improving blood pressure recovery via decreased levels of sFlt-1.
Interventions
Aspirin 81 mg 1 tablet by mouth. Participants randomized to receive aspirin in addition to standard blood pressure management will receive the study medication nightly at 20:00, with first dose initiated within 24 hours of delivery.
Sponsors
University of California, Irvine
MemorialCare Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcomes assessor will be blinded to study arms.
Intervention model description
Patients with preeclampsia will be randomized after delivery to receive either standard blood pressure control plus aspirin 81 mg or standard blood pressure control alone.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Preeclampsia with severe features diagnosed during delivery admission, as defined by ACOG criteria. * Pre- and postnatal care provided by the Long Beach Memorial Ob/Gyn resident or Maternal-Fetal Medicine clinic.
Exclusion criteria
* Patient age \<18 years old * Non-English or Non-Spanish speaking * Chronic hypertension diagnosed before 20 weeks' gestation * Known allergy, prior adverse reaction, or any medical condition in which aspirin is contraindicated (nasal polyps, gastric or duodenal ulcers, history of gastrointestinal bleeding, severe hepatic dysfunction) * Aspirin prescribed postpartum for any other medical condition * Bleeding disorder * Breastfeeding an infant with thrombocytopenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in sFlt-1 | 1 week postpartum | This outcome will determine the absolute change in sFlt-1, an anti-angiogenic protein implicated in the pathophysiology of preeclampsia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normotension (JNC) | 1 week postpartum | This outcome will measure the proportion of patients who achieve a blood pressure of \<130/80, as defined by JNC, without any further elevated values. |
| Time to normotension | 6 weeks postpartum | This outcome will assess the length of time in days to normotension after randomization. Normotension will be defined by both ACOG and JNC criteria. |
| Anti-hypertensive therapy | 6 weeks postpartum | This outcome will assess if additional or increased doses of anti-hypertensive therapies are needed following randomization. |
| Readmission | 6 weeks postpartum | This outcome will assess if a study participant is readmitted for blood pressure or preeclampsia related reasons following randomization. |
| Normotension (ACOG) | 1 week postpartum | This outcome will measure the proportion of patients who achieve a blood pressure of \<140/90, as defined by ACOG, without any further elevated values. |
| Enrollment feasibility | 1 week postpartum | This outcome will assess feasibility for future studies, defined as both the number of patients randomized by the number of patients eligible and the number of patients who completed the study protocol divided by the number of patients randomized. |
| Postpartum hemorrhage | 6 weeks postpartum | This safety outcome is defined as a postpartum hemorrhage of greater than 1 liter following randomization. |
| Postpartum bleeding requiring intervention | 6 weeks postpartum | This safety outcome is defined as postpartum bleeding requiring intervention (uterotonic administration, intrauterine balloon placement, dilation and curettage, or uterine artery embolization) following randomization. |
| Unplanned postpartum evaluation for bleeding | 6 weeks postpartum | This safety outcome is defined as the need for urgent evaluation for bleeding in the clinic/office, obstetrical triage unit, or emergency room for vaginal bleeding. |
| Adherence | 1 week postpartum | This outcome will assess for adherence to aspirin therapy in those randomized to the aspirin arm. This is defined as greater than 90% consumption of the prescribed doses. |
Countries
United States
Contacts
Primary ContactMegan C Oakes, MD MSCI
Backup ContactAshten B Waks, MD MSPH
Outcome results
None listed