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Aspirin and Preeclampsia

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ClinicalTrials.gov Identifier: NCT04479072
Recruitment Status : Recruiting
First Posted : July 21, 2020
Last Update Posted : March 12, 2021
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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 Global Longitudinal Strain (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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Investigator)
Masking Description: The study team and all randomized subjects will be blinded to which arm they were placed in. Subjects in the observational group will not be randomized and not given an intervention.
Primary Purpose: Prevention
Official Title: Aspirin to Prevent Cardiac Dysfunction in Preeclampsia
Actual Study Start Date : February 15, 2021
Estimated Primary Completion Date : January 1, 2026
Estimated Study Completion Date : February 28, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

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.



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.



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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
  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. Those who cannot provide consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04479072


Contacts
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Contact: Sajid Shahul, MD, PhD 773-398-2956 sshahul1@dacc.uchicago.edu
Contact: Edward H Fox 773-834-5234 efox1@bsd.uchicago.edu

Locations
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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
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT04479072    
Other Study ID Numbers: IRB18-1606
First Posted: July 21, 2020    Key Record Dates
Last Update Posted: March 12, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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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