<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04479072</url>
  </required_header>
  <id_info>
    <org_study_id>IRB18-1606</org_study_id>
    <nct_id>NCT04479072</nct_id>
  </id_info>
  <brief_title>Aspirin and Preeclampsia</brief_title>
  <official_title>Aspirin to Prevent Cardiac Dysfunction in Preeclampsia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-center, double-blind, randomized, placebo-controlled clinical trial.&#xD;
      Peripartum and postpartum Activin A are significantly elevated in women with preeclampsia.&#xD;
      Our hypothesis is that elevated Activin A levels reflect a remediable signal and that&#xD;
      reducing postpartum Activin A levels with aspirin therapy will improve (GLS) in preeclamptic&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of the main part of this trial is to mechanistically compare the effect&#xD;
      of postpartum aspirin therapy versus placebo in preeclamptic patients identified as high risk&#xD;
      for postpartum cardiac dysfunction using Activin A. The intent is to evaluate the effect of&#xD;
      selective treatment based on Activin A status rather than treatment for all postpartum&#xD;
      preeclamptic women.&#xD;
&#xD;
      After informed consent, 5cc of blood will be collected from the median cubital vein on&#xD;
      antepartum admission to labor and delivery for Activin A screening. The patient will be&#xD;
      subjected to a total of 2 such blood draws- a single draw at screening, one at their 6 month&#xD;
      postpartum visit. The member of the study team carrying out the blood draw will immediately&#xD;
      label the specimen in the presence of the subject, after the collection and before leaving&#xD;
      the patient's bedside, room, cubicle or surgical suite. The guidelines from, &quot;The University&#xD;
      of Chicago Medicine Policy and Procedure Manual - Phlebotomy Service Infection Control 04-26&quot;&#xD;
      will be followed for specimen collection and transport. Activin A levels based on our&#xD;
      previous data will be classified as elevated if greater than 23.74 ng/ml in the last&#xD;
      trimester of pregnancy (4). This threshold was selected on the basis of our prior data&#xD;
      suggesting an inflection point in the rate of abnormal GLS postpartum at this concentration.&#xD;
      Patients with elevated Activin A levels will be randomized to a placebo group receiving&#xD;
      routine postpartum cardiovascular standard of care or to an intervention arm with 81 mg daily&#xD;
      aspirin therapy added to care at their postpartum delivery stay. The rationale for only&#xD;
      randomizing women with elevated Activin A levels is that among women with an elevated Activin&#xD;
      A antepartum, 85% developed abnormalities in GLS at one year postpartum versus 25% in women&#xD;
      with non-elevated Activin A levels. Women whose Activin A levels are not elevated will&#xD;
      receive the same care as that provided to the placebo group and will also be followed for one&#xD;
      year (n=60). All other subjects who meet the criterial of elevated Activin A levels, will&#xD;
      either be randomized to the aspirin therapy group (N = 60) or a placebo group (N = 60). The&#xD;
      investigators choose postpartum Aspirin therapy post-delivery to avoid any immediate delivery&#xD;
      or C-section associated bleeding complications and to coincide with their postpartum&#xD;
      well-baby visit.&#xD;
&#xD;
      The investigator will determine the blood Activin A levels at 6 months after delivery,&#xD;
      measured using ELISA. The samples will be assayed for Activin A level using commercially&#xD;
      available ELISA kits (Ansh Labs; Webster, TX) following the manufacturer's recommendations.&#xD;
      Each sample will be run in triplicate and the values averaged. GLS at 6 months after delivery&#xD;
      will be measured using fully automated vendor-independent software that uses a computer&#xD;
      learning algorithm to facilitate endocardial border detection.&#xD;
&#xD;
      Mean arterial pressure, and other indices of systolic and diastolic function (ejection&#xD;
      fraction (EF), early filling/atrial contraction (E/A), deceleration time (DT), mitral annular&#xD;
      motion (E'), and left atrial volume index) measured at the baseline and 6 months postpartum.&#xD;
      Transthoracic echocardiograms will be performed and reported according to American Society of&#xD;
      Echocardiography guidelines. Ejection fraction and left atrial volume will be calculated&#xD;
      using the Simpson's biplane disc method. Left ventricular mass index (LVMI) will be&#xD;
      calculated using the area length method.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 15, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2025</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <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.&#xD;
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.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <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.&#xD;
The sub-study portion has no blinding attached to it</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in Activin A levels</measure>
    <time_frame>6 Months</time_frame>
    <description>The primary outcome will compare Activin A levels at 6 months between patients randomized to aspirin therapy versus placebo and the observational group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>GLS percentages</measure>
    <time_frame>6 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Arterial Pressure</measure>
    <time_frame>6 Months</time_frame>
    <description>Difference in mean arterial pressure in subjects, from their baseline to 6 month TTE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ejection Fraction %</measure>
    <time_frame>6 Months</time_frame>
    <description>Comparing the difference in the ejection fraction percentages, from the subjects baseline to 6 month TEE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Deceleration Time</measure>
    <time_frame>6 Months</time_frame>
    <description>Comparing the difference between deceleration time from subjects from their baseline to 6 month TTE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mitral Annular Motion</measure>
    <time_frame>6 Months</time_frame>
    <description>Comparing the difference between mitral annular motion, in millimeters (mm), from subjects baseline to 6 month TTE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left Atrial Volume Index</measure>
    <time_frame>6 Months</time_frame>
    <description>Comparing the difference between left atrial volume index, from the subjects baseline to 6 month TTE.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Preeclampsia Postpartum</condition>
  <arm_group>
    <arm_group_label>Intervention Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of aspirin 81 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of a placebo pill</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observational Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 81 mg</intervention_name>
    <description>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.</description>
    <arm_group_label>Intervention Arm</arm_group_label>
    <other_name>acetylsalicylic acid 81 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pregnant Adults between 18 and 45 years of age&#xD;
&#xD;
          2. Diagnosed with preeclampsia&#xD;
&#xD;
          3. Presenting for delivery with a singleton gestation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. We will exclude patients in labor&#xD;
&#xD;
          2. Patients with preexisting cardiomyopathy, chronic hypertension, ischemic or valvular&#xD;
             heart disease, pulmonary disease, diabetes mellitus, chronic kidney disease, multiple&#xD;
             gestation&#xD;
&#xD;
          3. Plan to deliver outside of the participating site&#xD;
&#xD;
          4. Co-enrolled in other trials that might affect the patients taking the study&#xD;
             medication, as determined by the PI.&#xD;
&#xD;
          5. Aspirin allergy&#xD;
&#xD;
          6. Clear indication for aspirin therapy or contraindication to aspirin therapy&#xD;
&#xD;
          7. Clinically significant conditions that might limit adherence to trial regimen (e.g.,&#xD;
             peptic ulcer disease, history of gastrointestinal bleeds, bleeding disorders)&#xD;
&#xD;
          8. Currently or planning on taking any nonsteroidal anti-inflammatory drugs while they&#xD;
             are participating in this study.&#xD;
&#xD;
          9. Those who cannot provide consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women with preeclampsia</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Sajid Shahul, MD, PhD</last_name>
    <phone>773-398-2956</phone>
    <email>sshahul1@dacc.uchicago.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Colleen Duncan, RN</last_name>
    <phone>7738342892</phone>
    <email>cduncan@bsd.uchicago.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Chicago Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sajid Shahul, MD, PhD</last_name>
      <phone>773-398-2956</phone>
      <email>sshahul1@dacc.uchicago.edu</email>
    </contact>
    <contact_backup>
      <last_name>John Dreixler, PhD</last_name>
      <phone>773-702-6700</phone>
      <email>JDreixle@dacc.uchicago.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sarosh Rana, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>November 23, 2022</last_update_submitted>
  <last_update_submitted_qc>November 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preeclampsia</keyword>
  <keyword>Postpartum GLS Levels</keyword>
  <keyword>Postpartum Activin A Levels</keyword>
  <keyword>Aspirin</keyword>
  <keyword>Cardiac Postpartum Therapy</keyword>
  <keyword>Hypertension</keyword>
  <keyword>Cardiovascular disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04479072
org study id: IRB18-1606
nct id: NCT04479072
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
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.
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.
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.
primary purpose: Prevention
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
measure: Difference in Activin A levels
time frame: 6 Months
description: The primary outcome will compare Activin A levels at 6 months between patients randomized to aspirin therapy versus placebo and the observational group.
measure: GLS percentages
time frame: 6 months
description: 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.
measure: Mean Arterial Pressure
time frame: 6 Months
description: Difference in mean arterial pressure in subjects, from their baseline to 6 month TTE
measure: Ejection Fraction %
time frame: 6 Months
description: Comparing the difference in the ejection fraction percentages, from the subjects baseline to 6 month TEE.
measure: Deceleration Time
time frame: 6 Months
description: Comparing the difference between deceleration time from subjects from their baseline to 6 month TTE.
measure: Mitral Annular Motion
time frame: 6 Months
description: Comparing the difference between mitral annular motion, in millimeters (mm), from subjects baseline to 6 month TTE.
measure: Left Atrial Volume Index
time frame: 6 Months
description: Comparing the difference between left atrial volume index, from the subjects baseline to 6 month TTE.
arm group label: Intervention Arm
arm group type: Active Comparator
description: 60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of aspirin 81 mg.
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: 60 subjects will be randomly assigned to this arm. The subjects in this arm will receive a daily dose of a placebo pill
arm group label: Observational Arm
arm group type: No Intervention
description: 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.
intervention type: Drug
intervention name: Aspirin 81 mg
description: 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.
arm group label: Intervention Arm
other name: acetylsalicylic acid 81 mg
intervention type: Drug
intervention name: Placebo
description: 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.
arm group label: Placebo Arm
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women with preeclampsia
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Sajid Shahul, MD, PhD
phone: 773-398-2956
email: sshahul1@dacc.uchicago.edu
last name: Colleen Duncan, RN
phone: 7738342892
email: cduncan@bsd.uchicago.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Pre-Eclampsia
mesh term: Aspirin
sharing ipd: No