Aspirin for Postpartum Patients With Preeclampsia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Acetylsalicylic Acid for Postpartum Preeclampsia: A Pilot Randomized Trial

Conditions
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Preeclampsia Postpartum

Intervention / Treatment
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* Drug: Aspirin 81Mg Ec Tab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard blood pressure control plus aspirin 81 mg<br>Standardized postpartum blood pressure control Aspirin 81 mg by mouth x 1 week post-delivery | Drug: Aspirin 81Mg Ec Tab<br>* 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.<br>|
| No Intervention: Standard blood pressure control<br>Standardized postpartum blood pressure control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in sFlt-1 | This outcome will determine the absolute change in sFlt-1, an anti-angiogenic protein implicated in the pathophysiology of preeclampsia. | 1 week postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normotension (ACOG) | 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. | 1 week postpartum | 
| Normotension (JNC) | 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. | 1 week postpartum | 
| Time to normotension | This outcome will assess the length of time in days to normotension after randomization. Normotension will be defined by both ACOG and JNC criteria. | 6 weeks postpartum | 
| Anti-hypertensive therapy | This outcome will assess if additional or increased doses of anti-hypertensive therapies are needed following randomization. | 6 weeks postpartum | 
| Readmission | This outcome will assess if a study participant is readmitted for blood pressure or preeclampsia related reasons following randomization. | 6 weeks postpartum | 
| Adherence | 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. | 1 week postpartum | 
| Enrollment feasibility | 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. | 1 week postpartum | 
| Postpartum hemorrhage | This safety outcome is defined as a postpartum hemorrhage of greater than 1 liter following randomization. | 6 weeks postpartum | 
| Postpartum bleeding requiring intervention | This safety outcome is defined as postpartum bleeding requiring intervention (uterotonic administration, intrauterine balloon placement, dilation and curettage, or uterine artery embolization) following randomization. | 6 weeks postpartum | 
| Unplanned postpartum evaluation for bleeding | 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. | 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preeclampsia, Postpartum, Aspirin, sFlt-1