<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/NCT03029091</url>
  </required_header>
  <id_info>
    <org_study_id>2015-9021</org_study_id>
    <secondary_id>U54AI117804</secondary_id>
    <nct_id>NCT03029091</nct_id>
  </id_info>
  <brief_title>An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)</brief_title>
  <official_title>A Preliminary Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Office of Rare Diseases (ORD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the safety and effectiveness of Losartan potassium in&#xD;
      subjects with eosinophilic esophagitis (EoE) including those with a connective tissue&#xD;
      disorder (CTD) and those without a CTD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this research study is to test the safety and effects (good and bad) of&#xD;
      Losartan potassium on participants with eosinophilic esophagitis (EoE). If a participant has&#xD;
      a connective tissue disorder (CTD) the researchers want to see what effects (good or bad)&#xD;
      Losartan has on EoE.&#xD;
&#xD;
      EoE is an inflammatory disease of the esophagus that is typically triggered by exposure to&#xD;
      food. Connective tissue disorders (CTDs) are disorders that affect the connective tissues in&#xD;
      the body such as tendons and ligaments.&#xD;
&#xD;
      A protein called transforming growth factor (TGF)-beta is associated with both EoE and CTD.&#xD;
      Losartan may decrease the amount of TGF-beta and therefore help EoE and CTD.&#xD;
&#xD;
      Losartan is a drug that is approved by the United States Food and Drug Administration (FDA)&#xD;
      for use in adults and children over 6 years of age who have high blood pressure. This&#xD;
      medication has not been studied in people with EoE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 23, 2017</start_date>
  <completion_date type="Actual">August 22, 2019</completion_date>
  <primary_completion_date type="Actual">July 22, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This study is an open-label study which means that all participants receive the study medicine.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Peak Eosinophil Count</measure>
    <time_frame>Baseline, 16 weeks</time_frame>
    <description>Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Serious and Grade 3 or Higher Adverse Events</measure>
    <time_frame>20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)</time_frame>
    <description>The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks</measure>
    <time_frame>16 weeks</time_frame>
    <description>Percent of participants in complete and partial histologic remission. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Histology Scoring System</measure>
    <time_frame>Baseline, 16 weeks</time_frame>
    <description>The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Endoscopic Reference Score</measure>
    <time_frame>Baseline, 16 weeks</time_frame>
    <description>The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in PEESS V2.0</measure>
    <time_frame>Baseline,16 weeks</time_frame>
    <description>The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline as completed by parent proxy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in PedsQL EoE</measure>
    <time_frame>Baseline, 16 weeks</time_frame>
    <description>The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Eosinophilic Esophagitis</condition>
  <arm_group>
    <arm_group_label>EoE +/- CTD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with EoE with and without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EoE + CTD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with EoE with CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EoE - CTD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with EoE without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Losartan Potassium</intervention_name>
    <description>Losartan potassium</description>
    <arm_group_label>EoE + CTD</arm_group_label>
    <arm_group_label>EoE +/- CTD</arm_group_label>
    <arm_group_label>EoE - CTD</arm_group_label>
    <other_name>Losartan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent/assent&#xD;
&#xD;
          -  Confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)&#xD;
&#xD;
          -  Does or does not have diagnosis of a connective tissue disorder (CTD)&#xD;
&#xD;
          -  Has been on a high dose of proton pump inhibitor (PPI) for at least 8 weeks prior to a&#xD;
             diagnostic endoscopy of EoE without histologic resolution (i.e., ≥ 15&#xD;
             eosinophils/HPF).&#xD;
&#xD;
          -  Maintain the same diet, swallowed steroid and PPI therapies throughout the duration of&#xD;
             the study&#xD;
&#xD;
          -  Female participants must be either:&#xD;
&#xD;
               1. Of non-childbearing potential (pre-menarchal or surgically sterile with&#xD;
                  documentation). OR&#xD;
&#xD;
               2. Have a negative urine pregnancy test at screening and at each monthly study&#xD;
                  visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any past or planned cardiac surgery.&#xD;
&#xD;
          -  An aortic root Z-score ≥ 3.0 on a previous echocardiogram.&#xD;
&#xD;
          -  Intolerance to Losartan&#xD;
&#xD;
          -  A mean blood pressure measurement (both systolic and diastolic) at screening that is&#xD;
             below the 2nd percentile for his/her age&#xD;
&#xD;
          -  Renal dysfunction&#xD;
&#xD;
          -  Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic&#xD;
             syndrome, Churg Strauss vasculitis, eosinophilic granuloma, or a parasitic infection).&#xD;
&#xD;
          -  A diagnosis of hepatic insufficiency (e.g., liver failure, history of liver&#xD;
             transplantation or persistent liver transaminase elevation).&#xD;
&#xD;
          -  A history of abnormal gastric or duodenal biopsy or documented gastrointestinal&#xD;
             disorders (e.g., Celiac Disease, Crohn's disease or Helicobacter pylori infection),&#xD;
             not including chronic gastritis, chronic duodenitis, mucosal eosinophilia or other&#xD;
             eosinophilic gastrointestinal disorders (EGIDs).&#xD;
&#xD;
          -  Use of anti-immunoglobulin (Ig)E monoclonal antibody (mAb), anti-tumor necrosis factor&#xD;
             (TNF) mAb, anti-IL-5 agents, or anti-IL-13 within 6 months prior to study entry&#xD;
&#xD;
          -  Use of methotrexate, cyclosporine, interferon α, or other systemic immunosuppressive&#xD;
             or immunomodulating agents within 3 months prior to the screening visit.&#xD;
&#xD;
          -  A stricture during endoscopy procedure that prevents passage of the endoscope&#xD;
&#xD;
          -  Taking or is planning to take an angiotensin receptor blocker (ARB),&#xD;
             angiotensin-converting enzyme inhibitor (ACEI), beta blocker (BB), or calcium-channel&#xD;
             blocker therapy at the screening visit or at any time during the study or has been&#xD;
             taking any of these medications for 3 months prior to the screening visit.&#xD;
&#xD;
          -  Taking or planning to take hydrochlorothiazide, digoxin, warfarin, cimetidine,&#xD;
             phenobarbital, rifampin, or fluconazole.&#xD;
&#xD;
          -  Taking or planning to take potassium supplements or salt substitutes containing&#xD;
             potassium.&#xD;
&#xD;
          -  A female participant who is pregnant or nursing or, if of childbearing potential, is&#xD;
             not using a medically accepted, effective method of birth control (e.g., condom,&#xD;
             oral/injectable/subcutaneous contraceptive, intrauterine device, or sexual&#xD;
             abstinence).&#xD;
&#xD;
          -  Participated/participating in any investigative drug or device study within 30 days&#xD;
             prior to study entry.&#xD;
&#xD;
          -  Participated/participating in any investigative biologics study within 3 months prior&#xD;
             to study entry.&#xD;
&#xD;
          -  Unable to be confirmed, active EoE (at Screening or within 12 weeks prior to&#xD;
             enrollment)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc E Rothenberg, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.rarediseasesnetwork.org/cms/CEGIR</url>
    <description>Study information on the Consortium for Eosinophilic Gastrointestinal Disorders (CEGIR) website</description>
  </link>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>July 21, 2020</results_first_submitted>
  <results_first_submitted_qc>July 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 10, 2020</results_first_posted>
  <last_update_submitted>August 21, 2020</last_update_submitted>
  <last_update_submitted_qc>August 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophagitis</mesh_term>
    <mesh_term>Eosinophilic Esophagitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03029091/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03029091/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from eosinophilic esophagitis specialty clinics (3 sites) in the USA between May 2017 and April 2019.</recruitment_details>
      <pre_assignment_details>17 participants screened, 2 excluded (2 met exclusion criteria), and 15 initiated the intervention</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>EoE + CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
        </group>
        <group group_id="P2">
          <title>EoE - CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>EoE + CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
        </group>
        <group group_id="B2">
          <title>EoE - CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</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="8"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="15"/>
          </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="10.4" spread="3.7"/>
                    <measurement group_id="B2" value="13.8" spread="5.0"/>
                    <measurement group_id="B3" value="12.0" spread="4.5"/>
                  </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="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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>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="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Peak Eosinophil Count</title>
        <description>Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.</description>
        <time_frame>Baseline, 16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak Eosinophil Count</title>
          <description>Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.</description>
          <population>Per protocol population (protocol violation excluded from data analysis)</population>
          <units>eosinophils per high power field</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.3" lower_limit="41.4" upper_limit="85.2"/>
                    <measurement group_id="O2" value="67.7" lower_limit="21.0" upper_limit="114.4"/>
                    <measurement group_id="O3" value="58.9" lower_limit="37.5" upper_limit="80.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.2" lower_limit="-36.9" upper_limit="14.5"/>
                    <measurement group_id="O2" value="-1.9" lower_limit="-40.6" upper_limit="36.9"/>
                    <measurement group_id="O3" value="-20.6" lower_limit="-65.2" upper_limit="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Serious and Grade 3 or Higher Adverse Events</title>
        <description>The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20</description>
        <time_frame>20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)</time_frame>
        <population>Intent to treat analysis including participants enrolled in the study</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Serious and Grade 3 or Higher Adverse Events</title>
          <description>The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20</description>
          <population>Intent to treat analysis including participants enrolled in the study</population>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 or higher adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks</title>
        <description>Percent of participants in complete and partial histologic remission. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.</description>
        <time_frame>16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks</title>
          <description>Percent of participants in complete and partial histologic remission. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.</description>
          <population>Per protocol population (protocol violation excluded from data analysis)</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete remission (≤ 1 eos/hpf)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="0" upper_limit="34"/>
                    <measurement group_id="O2" value="14" lower_limit="0" upper_limit="58"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial remission (2 - 14 eos/hpf)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21" lower_limit="5" upper_limit="51"/>
                    <measurement group_id="O2" value="14" lower_limit="0" upper_limit="58"/>
                    <measurement group_id="O3" value="29" lower_limit="4" upper_limit="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total Histology Scoring System</title>
        <description>The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.</description>
        <time_frame>Baseline, 16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Histology Scoring System</title>
          <description>The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.</description>
          <population>Per protocol population (protocol violation excluded from data analysis).</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline - Total HSS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.79" lower_limit="0.65" upper_limit="0.93"/>
                    <measurement group_id="O2" value="0.89" lower_limit="0.69" upper_limit="1.09"/>
                    <measurement group_id="O3" value="0.70" lower_limit="0.48" upper_limit="0.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change - Total HSS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" lower_limit="-0.28" upper_limit="0.10"/>
                    <measurement group_id="O2" value="-0.15" lower_limit="-0.47" upper_limit="0.17"/>
                    <measurement group_id="O3" value="-0.03" lower_limit="-0.33" upper_limit="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total Endoscopic Reference Score</title>
        <description>The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.</description>
        <time_frame>Baseline, 16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Endoscopic Reference Score</title>
          <description>The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.</description>
          <population>Per protocol population (protocol violation excluded from data analysis).</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline - EREFS Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" lower_limit="3.6" upper_limit="6.7"/>
                    <measurement group_id="O2" value="5.4" lower_limit="3.4" upper_limit="7.5"/>
                    <measurement group_id="O3" value="4.9" lower_limit="1.9" upper_limit="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change - EREFS Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" lower_limit="-2.6" upper_limit="0.0"/>
                    <measurement group_id="O2" value="-1.7" lower_limit="-3.2" upper_limit="-0.2"/>
                    <measurement group_id="O3" value="-0.9" lower_limit="-3.6" upper_limit="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in PEESS V2.0</title>
        <description>The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline as completed by parent proxy.</description>
        <time_frame>Baseline,16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in PEESS V2.0</title>
          <description>The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline as completed by parent proxy.</description>
          <population>Per protocol population (protocol violation excluded from data analysis)</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline - PEESS Total Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="7"/>
                    <count group_id="O3" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.9" lower_limit="15.5" upper_limit="44.4"/>
                    <measurement group_id="O2" value="32.7" lower_limit="6.36" upper_limit="59.0"/>
                    <measurement group_id="O3" value="26.7" lower_limit="6.3" upper_limit="47.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change - PEESS Total Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.7" lower_limit="-18.3" upper_limit="-1.1"/>
                    <measurement group_id="O2" value="-12.5" lower_limit="-31.2" upper_limit="6.2"/>
                    <measurement group_id="O3" value="-6.89" lower_limit="-15.3" upper_limit="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in PedsQL EoE</title>
        <description>The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.</description>
        <time_frame>Baseline, 16 weeks</time_frame>
        <population>Per protocol population (protocol violation excluded from data analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>EoE +/- CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O2">
            <title>EoE + CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
          </group>
          <group group_id="O3">
            <title>EoE - CTD</title>
            <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in PedsQL EoE</title>
          <description>The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.</description>
          <population>Per protocol population (protocol violation excluded from data analysis)</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline - PedsQL Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.4" lower_limit="64.2" upper_limit="84.5"/>
                    <measurement group_id="O2" value="73.3" lower_limit="58.7" upper_limit="87.8"/>
                    <measurement group_id="O3" value="75.6" lower_limit="55.3" upper_limit="96.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change - PedsQL Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" lower_limit="-0.1" upper_limit="13.5"/>
                    <measurement group_id="O2" value="4.8" lower_limit="-7.5" upper_limit="17.1"/>
                    <measurement group_id="O3" value="9.0" lower_limit="-0.4" upper_limit="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>EoE +/- CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan</description>
        </group>
        <group group_id="E2">
          <title>EoE + CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan</description>
        </group>
        <group group_id="E3">
          <title>EoE - CTD</title>
          <description>Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan</description>
        </group>
      </group_list>
      <serious_events>
        <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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Common Cold</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Transient Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rhinitis Infective</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Vasovagal reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Lightheaded</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marc E. Rothenberg, MD, PhD</name_or_title>
      <organization>Cincinnati Children's Hospital Medical Center</organization>
      <phone>513 636-7177</phone>
      <email>marc.rothenberg@cchmc.org</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/NCT03029091
org study id: 2015-9021
secondary id: U54AI117804
nct id: NCT03029091
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the safety and effectiveness of Losartan potassium in
      subjects with eosinophilic esophagitis (EoE) including those with a connective tissue
      disorder (CTD) and those without a CTD.
The purpose of this research study is to test the safety and effects (good and bad) of
      Losartan potassium on participants with eosinophilic esophagitis (EoE). If a participant has
      a connective tissue disorder (CTD) the researchers want to see what effects (good or bad)
      Losartan has on EoE.

      EoE is an inflammatory disease of the esophagus that is typically triggered by exposure to
      food. Connective tissue disorders (CTDs) are disorders that affect the connective tissues in
      the body such as tendons and ligaments.

      A protein called transforming growth factor (TGF)-beta is associated with both EoE and CTD.
      Losartan may decrease the amount of TGF-beta and therefore help EoE and CTD.

      Losartan is a drug that is approved by the United States Food and Drug Administration (FDA)
      for use in adults and children over 6 years of age who have high blood pressure. This
      medication has not been studied in people with EoE.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This study is an open-label study which means that all participants receive the study medicine.
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Peak Eosinophil Count
time frame: Baseline, 16 weeks
description: Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.
measure: Number of Serious and Grade 3 or Higher Adverse Events
time frame: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)
description: The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20
measure: Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks
time frame: 16 weeks
description: Percent of participants in complete and partial histologic remission. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.
measure: Change From Baseline in Total Histology Scoring System
time frame: Baseline, 16 weeks
description: The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.
measure: Change From Baseline in Total Endoscopic Reference Score
time frame: Baseline, 16 weeks
description: The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.
measure: Change From Baseline in PEESS V2.0
time frame: Baseline,16 weeks
description: The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline as completed by parent proxy.
measure: Change From Baseline in PedsQL EoE
time frame: Baseline, 16 weeks
description: The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.
arm group label: EoE +/- CTD
arm group type: Experimental
description: Participants with EoE with and without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
arm group label: EoE + CTD
arm group type: Experimental
description: Participants with EoE with CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
arm group label: EoE - CTD
arm group type: Experimental
description: Participants with EoE without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
intervention type: Drug
intervention name: Losartan Potassium
description: Losartan potassium
arm group label: EoE + CTD
arm group label: EoE +/- CTD
arm group label: EoE - CTD
other name: Losartan
criteria: 
gender: All
minimum age: 5 Years
maximum age: 25 Years
healthy volunteers: No
last name: Marc E Rothenberg, MD, PhD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
facility: 
facility: 
country: United States
url: https://www.rarediseasesnetwork.org/cms/CEGIR
description: Study information on the Consortium for Eosinophilic Gastrointestinal Disorders (CEGIR) website
responsible party type: Sponsor
mesh term: Esophagitis
mesh term: Eosinophilic Esophagitis
mesh term: Losartan
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 