Postpartum Low-Dose Aspirin and Preeclampsia

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to find out whether women with severe preeclampsia taking low-dose aspirin (LDA) for 3 weeks post-delivery will experience an improvement in endothelial function (measured as flow-mediated dilation - FMD) and severity of disease, as the effects of preeclampsia can persist postpartum. Women diagnosed with severe preeclampsia prior to delivery will be enrolled and randomized to receive either low-dose aspirin (81mg) or placebo to take daily for up to 3 weeks post-delivery. Exploratory objective includes healthy control postpartum patients without preeclampsia and not on LDA during pregnancy or postpartum in comparison with the primary study population affected by preeclampsia with severe features.

Detailed Description
-----------------
Preeclampsia is a serious disease of pregnancy that manifests with increased blood pressure and can affect all the organs in a woman's body. It usually develops after 20 weeks of pregnancy. There is an abnormal amount of protein in the urine and with worsening disease known as severe features, patients can have pain in the upper abdomen, changes in vision, fluid in the lungs, an intense headache, low number of platelets in the blood, and abnormal liver or kidney function. Very high blood pressure is also considered a severe feature. The exact cause of preeclampsia is unknown but women with the condition are at increased risk for complications during pregnancy, including seizures - eclampsia. Babies are at risk of being born premature because the only cure for preeclampsia is delivery. Women who have had preeclampsia are also at increased risk of cardiovascular and kidney disease later in life, including heart attack, stroke and high blood pressure. Studies show that women at high risk for preeclampsia, i.e., have had preeclampsia in a prior pregnancy, are carrying more than one fetus, have a history of high blood pressure, kidney disease or both, have certain medical problems such as diabetes, thrombophilia or lupus, have a modestly decreased risk of disease with daily intake of low-dose aspirin starting after 12 weeks of pregnancy. Due to the limited data available on the topic of LDA in preeclamptic patients in the postpartum period, particularly as applicable to the American population, the investigator intends to start with a small pilot study involving the collection of information on 10 women not exposed to study intervention. This will allow for confirmation of the sample size based on the baseline FMD measurements 2 days after delivery. Investigator will also explore a small sub-study to gather information regarding baseline FMD and biomarker values for healthy control postpartum patients, unaffected by preeclampsia and not on LDA during pregnancy or postpartum.

Official Title
-----------------
Low-Dose Aspirin in the Postpartum Period and Endothelial Function in Patients With Preeclampsia

Conditions
-----------------
Preeclampsia Postpartum

Intervention / Treatment
-----------------
* Drug: Aspirin tablet
* Drug: Placebo oral capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Singleton or Multiple gestation Maternal age >= 18 years 20 0/7 weeks gestation or greater Severe Preeclampsia diagnosed prior to delivery Exclusion Criteria: Aspirin use postpartum for other medical indication Lovenox, unfractionated heparin, or other anticoagulant use postpartum for an indication other than postoperative (in-house) Aspirin use within 7 days of planned initial FMD testing postpartum Hypersensitivity or allergy to Aspirin or other salicylates Hypersensitivity or allergy to nonsteroidal anti-inflammatory drugs (NSAIDs) - exception if taking LDA in pregnancy Nasal polyps Gastric or Duodenal ulcers, history of GI bleeding Severe hepatic dysfunction Bleeding disorders and diathesis Breastfeeding a newborn with low platelets (NAIT) For sub-study patients, inclusion and exclusion criteria will be the same, with the exception of diagnosis of severe preeclampsia prior to delivery (exclusion criterion for healthy controls group).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Preeclampsia patients will be recruited and randomized to receive either Aspirin or Placebo (n = 90). Additionally, there will be healthy patients (n = 10) recruited to collect the same set of data for comparison with no intervention.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low-Dose Aspirin (LDA) Intervention Group<br>Subjects diagnosed with severe preeclampsia prior to delivery (antepartum or intrapartum) will take 81mg of aspirin daily for up to 3 weeks postpartum, starting within 4 days after delivery. | Drug: Aspirin tablet<br>* Low dose aspirin, 81mg tablets, PO<br>* Other names: Aspirin;|
| Placebo Comparator: Placebo Control Group<br>Subjects diagnosed with severe preeclampsia prior to delivery (antepartum or intrapartum) will take placebo oral capsule daily for up to 3 weeks postpartum, starting within 4 days after delivery. | Drug: Placebo oral capsule<br>* Placebo oral capsule, PO<br>* Other names: Placebo;|
| No Intervention: Healthy Controls Group<br>Subjects who are healthy volunteers (n = 10) without severe preeclampsia prior to delivery. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flow-Mediated Dilation (FMD) | This is designed to measure if patients with preeclampsia with severe features diagnosed antepartum or intrapartum, will experience an increase in Flow-Mediated Dilation (FMD) - a measure of endothelial function - within 3 weeks after delivery when taking daily LDA in the postpartum period. | Up to 3 weeks postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic blood pressure | This is to measure if patients will experience a decrease in systolic blood pressure (SBP) within 3 weeks after delivery when taking daily LDA in the postpartum period. | Within 3 weeks postpartum | 
| Change in Diastolic blood pressure | This is to measure if patients will experience a decrease in diastolic blood pressure (DBP) within 3 weeks after delivery when taking daily LDA in the postpartum period. | Within 3 weeks postpartum | 
| Number of subjects with presentation of disease postpartum (symptoms, severe range BPs, lab abnormalities) | This is to measure if patients will experience decreased severity of disease when taking daily LDA in the postpartum period. | Up to 3 weeks postpartum | 
| Magnesium sulfate re-administration | This is to measure if patients will experience a decreased likelihood of receiving magnesium sulfate postpartum again when taking daily LDA in the postpartum period? | Up to 3 weeks postpartum | 
| Number of subjects with initiation of, increase in or addition of blood pressure medication | This is to measure if patients will experience a decreased rate in initiation of/ increase in/ addition of blood pressure medication postpartum when taking daily LDA in the postpartum period. | Up to 3 weeks postpartum | 
| Rate of hospital readmissions for postpartum preeclampsia | This is to measure if patients will experience a decreased rate of hospital readmissions for postpartum preeclampsia when taking daily LDA in the postpartum period. | Up to 3 weeks postpartum | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aspirin