Aspirin and Preeclampsia

Aspirin to Prevent Cardiac Dysfunction in Preeclampsia

This is a single-center, double-blind, randomized, placebo-controlled clinical trial. Peripartum and postpartum Activin A are significantly elevated in women with preeclampsia. Our hypothesis is that elevated Activin A levels reflect a remediable signal and that reducing postpartum Activin A levels with aspirin therapy will improve (GLS) in preeclamptic patients.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia Postpartum
• Intervention / Treatment: Drug: Aspirin 81 mg; Drug: Placebo

Detailed Description

The primary objective of the main part of this trial is to mechanistically compare the effect of postpartum aspirin therapy versus placebo in preeclamptic patients identified as high risk for postpartum cardiac dysfunction using Activin A. The intent is to evaluate the effect of selective treatment based on Activin A status rather than treatment for all postpartum preeclamptic women.

After informed consent, 5cc of blood will be collected from the median cubital vein on antepartum admission to labor and delivery for Activin A screening. The patient will be subjected to a total of 2 such blood draws- a single draw at screening, one at their 6 month postpartum visit. The member of the study team carrying out the blood draw will immediately label the specimen in the presence of the subject, after the collection and before leaving the patient's bedside, room, cubicle or surgical suite. The guidelines from, "The University of Chicago Medicine Policy and Procedure Manual - Phlebotomy Service Infection Control 04-26" will be followed for specimen collection and transport. Activin A levels based on our previous data will be classified as elevated if greater than 23.74 ng/ml in the last trimester of pregnancy (4). This threshold was selected on the basis of our prior data suggesting an inflection point in the rate of abnormal GLS postpartum at this concentration. Patients with elevated Activin A levels will be randomized to a placebo group receiving routine postpartum cardiovascular standard of care or to an intervention arm with 81 mg daily aspirin therapy added to care at their postpartum delivery stay. The rationale for only randomizing women with elevated Activin A levels is that among women with an elevated Activin A antepartum, 85% developed abnormalities in GLS at one year postpartum versus 25% in women with non-elevated Activin A levels. Women whose Activin A levels are not elevated will receive the same care as that provided to the placebo group and will also be followed for one year (n=60). All other subjects who meet the criterial of elevated Activin A levels, will either be randomized to the aspirin therapy group (N = 60) or a placebo group (N = 60). The investigators choose postpartum Aspirin therapy post-delivery to avoid any immediate delivery or C-section associated bleeding complications and to coincide with their postpartum well-baby visit.

The investigator will determine the blood Activin A levels at 6 months after delivery, measured using ELISA. The samples will be assayed for Activin A level using commercially available ELISA kits (Ansh Labs; Webster, TX) following the manufacturer's recommendations. Each sample will be run in triplicate and the values averaged. GLS at 6 months after delivery will be measured using fully automated vendor-independent software that uses a computer learning algorithm to facilitate endocardial border detection.

Mean arterial pressure, and other indices of systolic and diastolic function (ejection fraction (EF), early filling/atrial contraction (E/A), deceleration time (DT), mitral annular motion (E'), and left atrial volume index) measured at the baseline and 6 months postpartum. Transthoracic echocardiograms will be performed and reported according to American Society of Echocardiography guidelines. Ejection fraction and left atrial volume will be calculated using the Simpson's biplane disc method. Left ventricular mass index (LVMI) will be calculated using the area length method.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sajid Shahul, MD, PhD; Phone Number: 773-398-2956; Email: sshahul1@dacc.uchicago.edu
• Study Contact Backup: Name: Colleen Duncan, RN; Phone Number: 7738342892; Email: cduncan@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Hospital
      • Contact: Sajid Shahul, MD, PhD; Phone Number: 773-398-2956; Email: sshahul1@dacc.uchicago.edu
      • Contact: John Dreixler, PhD; Phone Number: 773-702-6700; Email: JDreixle@dacc.uchicago.edu
      • Sub-Investigator: Sarosh Rana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Pregnant Adults between 18 and 45 years of age
2. Diagnosed with preeclampsia
3. Presenting for delivery with a singleton gestation.

Exclusion Criteria:

1. We will exclude patients in labor
2. Patients with preexisting cardiomyopathy, chronic hypertension, ischemic or valvular heart disease, pulmonary disease, diabetes mellitus, chronic kidney disease, multiple gestation
3. Plan to deliver outside of the participating site
4. Co-enrolled in other trials that might affect the patients taking the study medication, as determined by the PI.
5. Aspirin allergy
6. Clear indication for aspirin therapy or contraindication to aspirin therapy
7. Clinically significant conditions that might limit adherence to trial regimen (e.g., peptic ulcer disease, history of gastrointestinal bleeds, bleeding disorders)
8. Currently or planning on taking any nonsteroidal anti-inflammatory drugs while they are participating in this study.
9. Those who cannot provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention Arm; 60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of aspirin 81 mg.	Drug: Aspirin 81 mg; Subjects in the interventional arm will receive a daily dose of aspirin 81 mg, starting at their baseline visit and to be taken up to their 6-month follow-up visit.; Other Names: acetylsalicylic acid 81 mg
Placebo Comparator: Placebo Arm; 60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of a placebo pill	Drug: Placebo; Subjects in this group will receive a daily dose of a placebo pill, starting at their baseline visit and to be taken up to their 6-month follow-up visit.
No Intervention: Observational Arm; 60 subjects will be placed in the observational arm. These subjects will not receive any intervention but will be followed and asked to return at the same time interval as the other 2 groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Activin A levels	The primary outcome will compare Activin A levels at 6 months between patients randomized to aspirin therapy versus placebo and the observational group.	6 Months
GLS percentages	The primary outcome will compare GLS levels as a percentage (%) at 6 months between patients randomized to aspirin therapy versus placebo and the observational group.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Arterial Pressure	Difference in mean arterial pressure in subjects, from their baseline to 6 month TTE	6 Months
Ejection Fraction %	Comparing the difference in the ejection fraction percentages, from the subjects baseline to 6 month TEE.	6 Months
Deceleration Time	Comparing the difference between deceleration time from subjects from their baseline to 6 month TTE.	6 Months
Mitral Annular Motion	Comparing the difference between mitral annular motion, in millimeters (mm), from subjects baseline to 6 month TTE.	6 Months
Left Atrial Volume Index	Comparing the difference between left atrial volume index, from the subjects baseline to 6 month TTE.	6 Months

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Anticipated): October 1, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 18, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): November 25, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Aspirin; Cardiovascular disease; Hypertension; Preeclampsia; Postpartum GLS Levels; Postpartum Activin A Levels; Cardiac Postpartum Therapy
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: IRB18-1606

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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.: Yes