Postpartum Low-Dose Aspirin and Preeclampsia

• ClinicalTrials.gov Identifier: NCT03667326
• Recruitment Status: Recruiting
• First Posted: September 12, 2018
• Last Update Posted: June 28, 2019
• Sponsor: Columbia University
• Information provided by (Responsible Party): Kirsten Lawrence Cleary, Columbia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Preeclampsia Postpartum	Drug: Aspirin; Drug: Placebo oral capsule	Phase 2

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, ie. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Prevention
• Official Title: Low-Dose Aspirin in the Postpartum Period and Endothelial Function in Patients With Preeclampsia
• Actual Study Start Date: January 7, 2019
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: April 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Low-Dose Aspirin (LDA) Intervention Group; 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; Low dose aspirin, 81mg tablets, PO
Placebo Comparator: Placebo Control Group; 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; Placebo oral capsule, PO; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Change in Flow-Mediated Dilation (FMD) [ Time Frame: Up to 3 weeks postpartum ]
   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.

Secondary Outcome Measures :

1. Change in Systolic blood pressure [ Time Frame: Within 3 weeks postpartum ]
   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.
2. Change in Diastolic blood pressure [ Time Frame: Within 3 weeks postpartum ]
   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.
3. Number of subjects with presentation of disease postpartum (symptoms, severe range BPs, lab abnormalities) [ Time Frame: Up to 3 weeks postpartum ]
   This is to measure if patients will experience decreased severity of disease when taking daily LDA in the postpartum period.
4. Magnesium sulfate re-administration [ Time Frame: Up to 3 weeks postpartum ]
   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?
5. Number of subjects with initiation of, increase in or addition of blood pressure medication [ Time Frame: Up to 3 weeks postpartum ]
   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.
6. Rate of hospital readmissions for postpartum preeclampsia [ Time Frame: Up to 3 weeks postpartum ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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 10 days of planned initial FMD testing postpartum
• Hypersensitivity or allergy to Aspirin or other salicylates
• Hypersensitivity or allergy to nonsteroidal anti-inflammatory drugs (NSAIDs)
• Nasal polyps
• Gastric or Duodenal ulcers, history of GI bleeding
• Severe hepatic dysfunction
• Bleeding disorders and diathesis
• Breastfeeding a newborn with low platelets (NAIT)

Contacts and Locations

Contacts

Contact: Kirsten Cleary, MD; 212-305-6293; klc2108@cumc.columbia.edu

Contact: Aleha Aziz, MD, MPH; 646-678-0289; aa4065@cumc.columbia.edu

Locations

United States, New York

Columbia University Irving Medical Center; Recruiting

New York, New York, United States, 10032

Contact: Aleha Aziz, MD 646-678-0289 aa4065@cumc.columbia.edu

Principal Investigator: Kirsten Cleary, MD

Sponsors and Collaborators

Columbia University

Investigators

• Principal Investigator: Kirsten Cleary, MD; Assistant Professor of Obstetrics and Gynecology at the Columbia

More Information

Publications:

The American College of Obstetricians and Gynecologists. Practice Advisory on Low-Dose Aspirin and Prevention of Preeclampsia: Updated Recommendations [Internet]. 2016. Available from: https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations

Costa AC, Reina-Couto M, Albino-Teixeira A, Sousa T. Aspirin and blood pressure: Effects when used alone or in combination with antihypertensive drugs. Rev Port Cardiol. 2017 Jul - Aug;36(7-8):551-567. doi: 10.1016/j.repc.2017.05.008. Epub 2017 Jul 3. Review. English, Portuguese.

• Responsible Party: Kirsten Lawrence Cleary, Assistant Professor of Obstetrics and Gynecology at the Columbia, Columbia University
• ClinicalTrials.gov Identifier: NCT03667326 History of Changes
• Other Study ID Numbers: AAAR9439
• First Posted: September 12, 2018
• Last Update Posted: June 28, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Kirsten Lawrence Cleary, Columbia University:

Aspirin

Additional relevant MeSH terms:

Pre-Eclampsia; Hypertension, Pregnancy-Induced; Pregnancy Complications; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics