Aspirin and Preeclampsia

• ClinicalTrials.gov Identifier: NCT04479072
• Recruitment Status: Recruiting
• First Posted: July 21, 2020
• Last Update Posted: November 25, 2022
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Preeclampsia Postpartum	Drug: Aspirin 81 mg; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment

Intervention Model Description

Main Study: Subjects will be randomized to two arms. One arm will receive a daily dose of aspirin 81 mg, starting at their baseline visit. The other arm will receive daily dose of placebo pill at their baseline visit. There will be a third arm, where subjects will not receive any study drug and will be considered the observational arm.

Sub-Study: Subjects who completed the main part of the study and choose to participate will be randomized once more into one of two arms for the purposes of the sub-study. One arm will receive the GDMP, which includes the RPM program. The other arm will not receive the GDMP and will continue thier usual standard of care course per thier treating physician.

• Masking: Double (Participant, Investigator)

Masking Description

The study team and all randomized subjects will be blinded to which arm they were placed in during the main part of the study. Subjects in the observational group will not be randomized and not given an intervention.

The sub-study portion has no blinding attached to it

• Primary Purpose: Prevention
• Official Title: Aspirin to Prevent Cardiac Dysfunction in Preeclampsia
• Actual Study Start Date: February 15, 2021
• Estimated Primary Completion Date: October 1, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Difference in Activin A levels [ Time Frame: 6 Months ]
   The primary outcome will compare Activin A levels at 6 months between patients randomized to aspirin therapy versus placebo and the observational group.
2. GLS percentages [ Time Frame: 6 months ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Pregnant women with preeclampsia
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Sajid Shahul, MD, PhD; 773-398-2956; sshahul1@dacc.uchicago.edu

Contact: Colleen Duncan, RN; 7738342892; cduncan@bsd.uchicago.edu

Locations

United States, Illinois

University of Chicago Hospital; Recruiting

Chicago, Illinois, United States, 60637

Contact: Sajid Shahul, MD, PhD 773-398-2956 sshahul1@dacc.uchicago.edu

Contact: John Dreixler, PhD 773-702-6700 JDreixle@dacc.uchicago.edu

Sub-Investigator: Sarosh Rana, MD

Sponsors and Collaborators

University of Chicago

More Information

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT04479072
• Other Study ID Numbers: IRB18-1606
• First Posted: July 21, 2020
• Last Update Posted: November 25, 2022
• Last Verified: November 2022

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.: Yes

Keywords provided by University of Chicago:

Preeclampsia; Postpartum GLS Levels; Postpartum Activin A Levels; Aspirin; Cardiac Postpartum Therapy; Hypertension; Cardiovascular disease

Additional relevant MeSH terms:

Pre-Eclampsia; Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; 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