<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/NCT04402385</url>
  </required_header>
  <id_info>
    <org_study_id>2000028023</org_study_id>
    <nct_id>NCT04402385</nct_id>
  </id_info>
  <brief_title>Aspirin to Prevent Preeclampsia in Women With Elevated Blood Pressure and Stage 1 Hypertension (ASPPIRE)</brief_title>
  <official_title>Aspirin to Prevent Preeclampsia in Women With Elevated Blood Pressure and Stage 1 Hypertension (ASPPIRE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if low dose aspirin reduces the incidence of hypertensive disorders of pregnancy&#xD;
      (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome) in pregnant women&#xD;
      with stage 1 hypertension and elevated blood pressure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At the baseline visit, women will go through informed consent and review of study&#xD;
      eligibility. Objectives of the study, participation requirements, eligibility inclusion and&#xD;
      exclusion will be reviewed in detail. If these are not met, the woman is excluded from the&#xD;
      study. If she meets inclusion criteria, a checklist of exclusion criteria will be reviewed.&#xD;
      If any exclusions are met, the woman is excluded from the study. The consent form will be&#xD;
      reviewed in detail. If the woman consents and signs all pages of the form, randomization&#xD;
      follows.&#xD;
&#xD;
      Randomization will be done in a 1:1 allocation ratio between the treatment and placebo arms,&#xD;
      stratified by blood pressure group (elevated blood pressure and stage 1 hypertension). A&#xD;
      computer algorithm will assign participant based on random permuted blocks design with block&#xD;
      size between 2-4 within each strata. Each participant will have an assigned Study ID number&#xD;
      that is linked to their random assignment.&#xD;
&#xD;
      Participants will be contacted by telephone 1 week after randomization. The purpose of this&#xD;
      visit is to ensure the participant has received study medication and initiated the regimen.&#xD;
&#xD;
      The third encounter will be 6 weeks (+/- 1week) after randomization in person to coincide&#xD;
      with routine prenatal visit or via telephone. The purpose of this study visit is to review&#xD;
      their pregnancy course, use of study medications, any side effects, difficulties with the&#xD;
      study, and have opportunities to make comments and/or ask questions. The participants will be&#xD;
      asked to bring their study medication for pill count at the time of this encounter, if the&#xD;
      study visit is able to be performed in person. Study participants will continue their routine&#xD;
      prenatal care with pregnancy management performed routinely per their provider.&#xD;
&#xD;
      The fourth encounter will be 16 weeks (+/- 1week) after randomization in person to coincide&#xD;
      with routine prenatal visit or via telephone. If the participant is already delivered by this&#xD;
      time, the visit will be performed via telephone postpartum. The purpose of this study visit&#xD;
      is to review their pregnancy course, use of study medications, any side effects, difficulties&#xD;
      with the study, and have opportunities to make comments and/or ask questions. The&#xD;
      participants will be asked to bring their study medication for pill count at the time of this&#xD;
      encounter, if the study visit is able to be performed in person.&#xD;
&#xD;
      The rest of the study will be conducted via chart review. Each prenatal visit will be&#xD;
      reviewed for blood pressure, evaluation of symptoms, review of any laboratory and/or imaging&#xD;
      results. New diagnoses, medications, and hospital admissions will be documented.&#xD;
&#xD;
      Delivery records will be abstracted for outcomes listed below. Neonatal records will be&#xD;
      reviewed from birth until 1 year of age. Neonatal and infant chart abstraction will include&#xD;
      birthweight, Apgar scores, hospital course, problem visit, diagnoses, medications, emergency&#xD;
      department visits, and hospitalizations. Participant's postpartum course will be reviewed for&#xD;
      1 year postpartum, including outpatient visits, emergency department visits, and any&#xD;
      hospitalizations.&#xD;
&#xD;
      The study will be performed by an intent-to-treat analysis. Thus, even women who discontinue&#xD;
      study medication will be included in final analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Unable to recruit.&#xD;
  </why_stopped>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Actual">June 22, 2022</completion_date>
  <primary_completion_date type="Actual">June 22, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Development of Hypertensive Disorder</measure>
    <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of any hypertensive disorder of pregnancy (gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome). This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Development of Gestational Hypertension</measure>
    <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of gestational hypertension. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Preeclampsia</measure>
    <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of preeclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Preeclampsia- 37 Weeks</measure>
    <time_frame>up to 37 weeks gestation</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 37 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Preeclampsia- 34 Weeks</measure>
    <time_frame>up to 34 weeks gestation</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 34 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Eclampsia</measure>
    <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of eclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of HELLP Syndrome</measure>
    <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
    <description>This measure is operationally defined as a yes/no response to the development of HELLP syndrome. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spontaneous Preterm Delivery</measure>
    <time_frame>Up to 37 weeks</time_frame>
    <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 37 weeks of pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spontaneous Preterm Delivery</measure>
    <time_frame>Up to 34 weeks</time_frame>
    <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 34 weeks of pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal Growth Restriction</measure>
    <time_frame>after 20 weeks gestation until delivery</time_frame>
    <description>Fetal growth restriction is estimated fetal weight &lt;10th percentile for gestational age by Hadlock criteria with Yale New Haven Health practice-specific growth curves.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birthweight</measure>
    <time_frame>day of life 0</time_frame>
    <description>Birthweight small for gestational age (&lt;10% by sex-specific World Health Organization growth charts)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal ICU Admission</measure>
    <time_frame>Birth until 1 year of age</time_frame>
    <description>Neonatal ICU admission is operationally defined as a yes/no to whether a newborn was admitted to the neonatal ICU admission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stillbirth</measure>
    <time_frame>after 20 weeks gestation until delivery</time_frame>
    <description>Stillbirth is operationally defined as a fetal death before or during delivery (corrected when results were entered)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal Adverse Events</measure>
    <time_frame>Birth until 1 year of age</time_frame>
    <description>Neonatal adverse events are operationally defined as a composite yes/no response of any of the following: need for respiratory support, necrotizing enterocolitis, neonatal sepsis, retinopathy of prematurity, intraventricular hemorrhage, neonatal death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placental Abruption</measure>
    <time_frame>after 20 weeks gestation until delivery</time_frame>
    <description>Placental abruption is operationally defined as a yes/no response to a placental abruption verified either clinically or as seen on pathologic placental examination.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Pre-Eclampsia</condition>
  <condition>Stage 1 Hypertension</condition>
  <condition>Elevated Blood Pressure</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to 81 mg of Aspirin daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to placebo daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 81 mg</intervention_name>
    <description>Participants randomized to 81 mg of Aspirin daily</description>
    <arm_group_label>Aspirin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants randomized to placebo daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Elevated blood pressure (At least 2 systolic BP 120-129 mm Hg within 1 year&#xD;
             pre-pregnancy until 20 weeks gestational age on at least 2 separate healthcare&#xD;
             encounters) or Stage 1 hypertension (At least 2 systolic BP 130-139 and/or diastolic&#xD;
             BP 80-89 within 1 year pre-pregnancy until 20 weeks gestational age on at least 2&#xD;
             separate healthcare encounters)&#xD;
&#xD;
          -  Speaks English or Spanish&#xD;
&#xD;
          -  Informed and written consent&#xD;
&#xD;
          -  Confirmed single live intrauterine pregnancy (confirmed by positive cardiac motion by&#xD;
             transvaginal or transabdominal ultrasound)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic hypertension&#xD;
&#xD;
          -  Pre-gestational diabetes&#xD;
&#xD;
          -  Chronic renal disease&#xD;
&#xD;
             - diagnosis of stage 1 chronic kidney disease or higher and/or GFR &lt;60 mL/min with&#xD;
             duration at least 3 months and/or history of kidney transplantation and/or undergoing&#xD;
             peritoneal or hemodialysis&#xD;
&#xD;
          -  Systemic lupus erythematous&#xD;
&#xD;
          -  Antiphospholipid antibody syndrome (diagnosis made by having 1 or more clinical&#xD;
             criteria and 1 or more laboratory criteria)&#xD;
&#xD;
               -  Clinical criteria: venous thrombosis, arterial thrombosis, obstetric&#xD;
                  complications (3 or more unexplained consecutive spontaneous abortions &lt;10 weeks&#xD;
                  gestation, 1 or more unexplained deaths of a morphologically normal fetus after&#xD;
                  10 weeks gestation, 1 or more premature births before 34 weeks gestation&#xD;
                  attributable to placental insufficiency, including severe preeclampsia or fetal&#xD;
                  growth restriction)&#xD;
&#xD;
               -  Laboratory criteria: lupus anticoagulant, anti-cardiolipin IgG or IgM with titer&#xD;
                  &gt;99th percentile, anti-beta 2 glycoprotein IgG or IgM with titer &gt;99th&#xD;
                  percentile. Laboratory result must be positive twice at least 12 weeks apart&#xD;
&#xD;
          -  Multifetal gestation&#xD;
&#xD;
          -  20 weeks gestation at time of randomization based on American College of Obstetricians&#xD;
             and Gynecologists dating criteria. Dating will be based on last menstrual period (LMP)&#xD;
             if regular, sure LMP is available that agrees with ultrasound dating. Otherwise,&#xD;
             earliest ultrasound will be used for dating purposes.&#xD;
&#xD;
          -  Prior history of hypertensive disorder of pregnancy&#xD;
&#xD;
          -  Current pregnancy with known chromosomal, genetic, major malformations or fetal&#xD;
             demise, or planned termination of pregnancy&#xD;
&#xD;
          -  Women with contraindications to taking aspirin (bleeding diathesis such as Von&#xD;
             Willebrand's disease, peptic ulcer disease, aspirin hypersensitivity, nasal polyps,&#xD;
             asthma with aspirin-induced bronchospasm, severe liver disease).&#xD;
&#xD;
          -  Concurrent participation in another study that influences risk of preeclampsia&#xD;
&#xD;
          -  Women who do not plan to deliver within the YNHH system&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Olga Grechukhina, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hillart Hosier, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06512</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <results_first_submitted>June 21, 2023</results_first_submitted>
  <results_first_submitted_qc>June 21, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 11, 2023</results_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aspirin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</mesh_term>
    <mesh_term>Eclampsia</mesh_term>
    <mesh_term>Hypertension</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>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 8, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04402385/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Aspirin</title>
          <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants from the initially enrolled that delivered successfully.</population>
      <group_list>
        <group group_id="B1">
          <title>Aspirin</title>
          <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.0" spread="6.4"/>
                    <measurement group_id="B2" value="29.8" spread="6.6"/>
                    <measurement group_id="B3" value="28.9" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Development of Hypertensive Disorder</title>
        <description>This measure is operationally defined as a yes/no response to the development of any hypertensive disorder of pregnancy (gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome). This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
        <population>All enrolled participants that successfully delivered.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Hypertensive Disorder</title>
          <description>This measure is operationally defined as a yes/no response to the development of any hypertensive disorder of pregnancy (gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome). This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of Gestational Hypertension</title>
        <description>This measure is operationally defined as a yes/no response to the development of gestational hypertension. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
        <population>All enrolled participants that successfully delivered.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Gestational Hypertension</title>
          <description>This measure is operationally defined as a yes/no response to the development of gestational hypertension. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of Preeclampsia</title>
        <description>This measure is operationally defined as a yes/no response to the development of preeclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
        <population>All enrolled participants that successfully delivered.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Preeclampsia</title>
          <description>This measure is operationally defined as a yes/no response to the development of preeclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of Preeclampsia- 37 Weeks</title>
        <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 37 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>up to 37 weeks gestation</time_frame>
        <population>All enrolled participants that successfully delivered.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Preeclampsia- 37 Weeks</title>
          <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 37 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of Preeclampsia- 34 Weeks</title>
        <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 34 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>up to 34 weeks gestation</time_frame>
        <population>All enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Preeclampsia- 34 Weeks</title>
          <description>This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 34 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of Eclampsia</title>
        <description>This measure is operationally defined as a yes/no response to the development of eclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
        <population>All enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of Eclampsia</title>
          <description>This measure is operationally defined as a yes/no response to the development of eclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Development of HELLP Syndrome</title>
        <description>This measure is operationally defined as a yes/no response to the development of HELLP syndrome. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
        <time_frame>after 20 weeks gestation until 6 weeks postpartum</time_frame>
        <population>All enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Development of HELLP Syndrome</title>
          <description>This measure is operationally defined as a yes/no response to the development of HELLP syndrome. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.</description>
          <population>All enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spontaneous Preterm Delivery</title>
        <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 37 weeks of pregnancy.</description>
        <time_frame>Up to 37 weeks</time_frame>
        <population>All enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Spontaneous Preterm Delivery</title>
          <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 37 weeks of pregnancy.</description>
          <population>All enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spontaneous Preterm Delivery</title>
        <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 34 weeks of pregnancy.</description>
        <time_frame>Up to 34 weeks</time_frame>
        <population>All enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Spontaneous Preterm Delivery</title>
          <description>This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 34 weeks of pregnancy.</description>
          <population>All enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fetal Growth Restriction</title>
        <description>Fetal growth restriction is estimated fetal weight &lt;10th percentile for gestational age by Hadlock criteria with Yale New Haven Health practice-specific growth curves.</description>
        <time_frame>after 20 weeks gestation until delivery</time_frame>
        <population>All infants born to enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Fetal Growth Restriction</title>
          <description>Fetal growth restriction is estimated fetal weight &lt;10th percentile for gestational age by Hadlock criteria with Yale New Haven Health practice-specific growth curves.</description>
          <population>All infants born to enrolled participants that successfully delivered while on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Birthweight</title>
        <description>Birthweight small for gestational age (&lt;10% by sex-specific World Health Organization growth charts)</description>
        <time_frame>day of life 0</time_frame>
        <population>All infants born from enrolled participants that successfully delivered while on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Birthweight</title>
          <description>Birthweight small for gestational age (&lt;10% by sex-specific World Health Organization growth charts)</description>
          <population>All infants born from enrolled participants that successfully delivered while on study.</population>
          <units>weight in grams</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3320.95" spread="390.47"/>
                    <measurement group_id="O2" value="3271.57" spread="609.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neonatal ICU Admission</title>
        <description>Neonatal ICU admission is operationally defined as a yes/no to whether a newborn was admitted to the neonatal ICU admission.</description>
        <time_frame>Birth until 1 year of age</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Neonatal ICU Admission</title>
          <description>Neonatal ICU admission is operationally defined as a yes/no to whether a newborn was admitted to the neonatal ICU admission.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>NICU Admission = Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NICU Admission = No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stillbirth</title>
        <description>Stillbirth is operationally defined as a fetal death before or during delivery (corrected when results were entered)</description>
        <time_frame>after 20 weeks gestation until delivery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Stillbirth</title>
          <description>Stillbirth is operationally defined as a fetal death before or during delivery (corrected when results were entered)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neonatal Adverse Events</title>
        <description>Neonatal adverse events are operationally defined as a composite yes/no response of any of the following: need for respiratory support, necrotizing enterocolitis, neonatal sepsis, retinopathy of prematurity, intraventricular hemorrhage, neonatal death.</description>
        <time_frame>Birth until 1 year of age</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Neonatal Adverse Events</title>
          <description>Neonatal adverse events are operationally defined as a composite yes/no response of any of the following: need for respiratory support, necrotizing enterocolitis, neonatal sepsis, retinopathy of prematurity, intraventricular hemorrhage, neonatal death.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Placental Abruption</title>
        <description>Placental abruption is operationally defined as a yes/no response to a placental abruption verified either clinically or as seen on pathologic placental examination.</description>
        <time_frame>after 20 weeks gestation until delivery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aspirin</title>
            <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Placental Abruption</title>
          <description>Placental abruption is operationally defined as a yes/no response to a placental abruption verified either clinically or as seen on pathologic placental examination.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From 20 weeks gestational up to 1 year following birth</time_frame>
      <desc>Adverse event reporting only for parents that delivered while on study and their children born on study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Aspirin - Parent</title>
          <description>Participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
        </group>
        <group group_id="E2">
          <title>Aspirin - Infant</title>
          <description>Children of participants randomized to 81 mg of Aspirin daily&#xD;
Aspirin 81 mg: Participants randomized to 81 mg of Aspirin daily</description>
        </group>
        <group group_id="E3">
          <title>Placebo - Parent</title>
          <description>Participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
        </group>
        <group group_id="E4">
          <title>Placebo - Infant</title>
          <description>Children of participants randomized to placebo daily&#xD;
Placebo: Participants randomized to placebo daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Nosebleed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Microcephaly</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Laryngomalacia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Postpartum Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Syncytial Virus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Olga Grechukhina, MD: Assistant Professor of Obstetrics, Gynecology &amp; Reproductive Sciences</name_or_title>
      <organization>Yale School of Medicine</organization>
      <phone>(203) 785-3091</phone>
      <email>olga.grechukhina@yale.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04402385
org study id: 2000028023
nct id: NCT04402385
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To determine if low dose aspirin reduces the incidence of hypertensive disorders of pregnancy
      (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome) in pregnant women
      with stage 1 hypertension and elevated blood pressure.
At the baseline visit, women will go through informed consent and review of study
      eligibility. Objectives of the study, participation requirements, eligibility inclusion and
      exclusion will be reviewed in detail. If these are not met, the woman is excluded from the
      study. If she meets inclusion criteria, a checklist of exclusion criteria will be reviewed.
      If any exclusions are met, the woman is excluded from the study. The consent form will be
      reviewed in detail. If the woman consents and signs all pages of the form, randomization
      follows.

      Randomization will be done in a 1:1 allocation ratio between the treatment and placebo arms,
      stratified by blood pressure group (elevated blood pressure and stage 1 hypertension). A
      computer algorithm will assign participant based on random permuted blocks design with block
      size between 2-4 within each strata. Each participant will have an assigned Study ID number
      that is linked to their random assignment.

      Participants will be contacted by telephone 1 week after randomization. The purpose of this
      visit is to ensure the participant has received study medication and initiated the regimen.

      The third encounter will be 6 weeks (+/- 1week) after randomization in person to coincide
      with routine prenatal visit or via telephone. The purpose of this study visit is to review
      their pregnancy course, use of study medications, any side effects, difficulties with the
      study, and have opportunities to make comments and/or ask questions. The participants will be
      asked to bring their study medication for pill count at the time of this encounter, if the
      study visit is able to be performed in person. Study participants will continue their routine
      prenatal care with pregnancy management performed routinely per their provider.

      The fourth encounter will be 16 weeks (+/- 1week) after randomization in person to coincide
      with routine prenatal visit or via telephone. If the participant is already delivered by this
      time, the visit will be performed via telephone postpartum. The purpose of this study visit
      is to review their pregnancy course, use of study medications, any side effects, difficulties
      with the study, and have opportunities to make comments and/or ask questions. The
      participants will be asked to bring their study medication for pill count at the time of this
      encounter, if the study visit is able to be performed in person.

      The rest of the study will be conducted via chart review. Each prenatal visit will be
      reviewed for blood pressure, evaluation of symptoms, review of any laboratory and/or imaging
      results. New diagnoses, medications, and hospital admissions will be documented.

      Delivery records will be abstracted for outcomes listed below. Neonatal records will be
      reviewed from birth until 1 year of age. Neonatal and infant chart abstraction will include
      birthweight, Apgar scores, hospital course, problem visit, diagnoses, medications, emergency
      department visits, and hospitalizations. Participant's postpartum course will be reviewed for
      1 year postpartum, including outpatient visits, emergency department visits, and any
      hospitalizations.

      The study will be performed by an intent-to-treat analysis. Thus, even women who discontinue
      study medication will be included in final analyses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Development of Hypertensive Disorder
time frame: after 20 weeks gestation until 6 weeks postpartum
description: This measure is operationally defined as a yes/no response to the development of any hypertensive disorder of pregnancy (gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome). This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of Gestational Hypertension
time frame: after 20 weeks gestation until 6 weeks postpartum
description: This measure is operationally defined as a yes/no response to the development of gestational hypertension. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of Preeclampsia
time frame: after 20 weeks gestation until 6 weeks postpartum
description: This measure is operationally defined as a yes/no response to the development of preeclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of Preeclampsia- 37 Weeks
time frame: up to 37 weeks gestation
description: This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 37 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of Preeclampsia- 34 Weeks
time frame: up to 34 weeks gestation
description: This measure is operationally defined as a yes/no response to the development of preeclampsia at less than 34 weeks of pregnancy. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of Eclampsia
time frame: after 20 weeks gestation until 6 weeks postpartum
description: This measure is operationally defined as a yes/no response to the development of eclampsia. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Development of HELLP Syndrome
time frame: after 20 weeks gestation until 6 weeks postpartum
description: This measure is operationally defined as a yes/no response to the development of HELLP syndrome. This is defined by American College of Obstetricians and Gynecologists diagnostic criteria.
measure: Spontaneous Preterm Delivery
time frame: Up to 37 weeks
description: This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 37 weeks of pregnancy.
measure: Spontaneous Preterm Delivery
time frame: Up to 34 weeks
description: This measure is operationally defined as a yes/no response to a spontaneous preterm delivery up to 34 weeks of pregnancy.
measure: Fetal Growth Restriction
time frame: after 20 weeks gestation until delivery
description: Fetal growth restriction is estimated fetal weight <10th percentile for gestational age by Hadlock criteria with Yale New Haven Health practice-specific growth curves.
measure: Birthweight
time frame: day of life 0
description: Birthweight small for gestational age (<10% by sex-specific World Health Organization growth charts)
measure: Neonatal ICU Admission
time frame: Birth until 1 year of age
description: Neonatal ICU admission is operationally defined as a yes/no to whether a newborn was admitted to the neonatal ICU admission.
measure: Stillbirth
time frame: after 20 weeks gestation until delivery
description: Stillbirth is operationally defined as a fetal death before or during delivery (corrected when results were entered)
measure: Neonatal Adverse Events
time frame: Birth until 1 year of age
description: Neonatal adverse events are operationally defined as a composite yes/no response of any of the following: need for respiratory support, necrotizing enterocolitis, neonatal sepsis, retinopathy of prematurity, intraventricular hemorrhage, neonatal death.
measure: Placental Abruption
time frame: after 20 weeks gestation until delivery
description: Placental abruption is operationally defined as a yes/no response to a placental abruption verified either clinically or as seen on pathologic placental examination.
arm group label: Aspirin
arm group type: Experimental
description: Participants randomized to 81 mg of Aspirin daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized to placebo daily
intervention type: Drug
intervention name: Aspirin 81 mg
description: Participants randomized to 81 mg of Aspirin daily
arm group label: Aspirin
intervention type: Drug
intervention name: Placebo
description: Participants randomized to placebo daily
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olga Grechukhina, MD
role: Principal Investigator
affiliation: Yale University
last name: Hillart Hosier, MD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pre-Eclampsia
mesh term: Eclampsia
mesh term: Hypertension
mesh term: Aspirin
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 